Published Work


Bioenergetics underlying single-cell migration on aligned nanofiber scaffolds

February 19, 2020

Cell migration is centrally involved in a myriad of physiological processes, including morphogenesis, wound healing, tissue repair, and metastatic growth. The bioenergetics that underlie migratory behavior are not fully understood, in part because of variations in cell culture media and utilization of experimental cell culture systems that do not model physiological connective extracellular fibrous networks. In this study, we evaluated the bioenergetics of C2C12 myoblast migration and force production on fibronectin-coated nanofiber scaffolds of controlled diameter and alignment, fabricated using a nonelectrospinning spinneret-based tunable engineered parameters (STEP) platform. The contribution of various metabolic pathways to cellular migration was determined using inhibitors of cellular respiration, ATP synthesis, glycolysis, or glucose uptake. Despite immediate effects on oxygen consumption, mitochondrial inhibition only modestly reduced cell migration velocity, whereas inhibitors of glycolysis and cellular glucose uptake led to striking decreases in migration. The migratory metabolic sensitivity was modifiable based on the substrates present in cell culture media. Cells cultured in galactose (instead of glucose) showed substantial migratory sensitivity to mitochondrial inhibition. We used nanonet force microscopy to determine the bioenergetic factors responsible for single-cell force production and observed that neither mitochondrial nor glycolytic inhibition altered single-cell force production. These data suggest that myoblast migration is heavily reliant on glycolysis in cells grown in conventional media. These studies have wide-ranging implications for the causes, consequences, and putative therapeutic treatments aimed at cellular migration.

Cancer Cells Sense Fibers by Coiling on

Cancer Cells Sense Fibers by Coiling on them in a Curvature-Dependent Manner

September 27, 2019

Metastatic cancer cells sense the complex and heterogeneous fibrous extracellular matrix (ECM) byformation of protrusions, and our knowledge of how cells physically recognize these fibers remainsin its infancy. Here, using suspended ECM-mimicking isodiameter fibers ranging from 135 to1,000 nm, we show that metastatic breast cancer cells sense fiber diameters differentially bycoiling(wrapping-around) on them in a curvature-dependent manner, whereas non-tumorigenic cells exhibitdiminishedcoiling. We report thatcoilingoccurs at the tip of growing protrusions and thecoil widthandcoiling rateincrease in a curvature-dependent manner, but time to maximumcoil widthoccurs bi-phasically. Interestingly, bundles of 135-nm diameter fibers recovercoiling widthandrateon 1,000-nm-diameter fibers.Coilingalso coincides with curvature-dependent persistent and ballistic transportof endogenous granules inside the protrusions. Altogether, our results lay the groundwork to link bio-physical sensing with biological signaling to quantitate pro- and anti-invasive fibrous environments.

Science Lab

Inositol polyphosphate multikinase is a metformin target that regulates cell migration

October 30, 2019

Metformin has been shown to alter cell adhesion protein expression, which is thought to play a role in its observed antitumor properties. We found that metformin treatment down-regulated integrin β1 concomitant with the loss of inositol polyphosphate multikinase (IPMK) in murine myocytes, adipocytes, and hepatocytes. To determine if IPMK was upstream of integrin β1 expression, we examined IPMK−/− mouse embryonic fibroblast cells and found that integrins β1 and β3 gene expression was reduced by half, relative to wild-type cells, whereas focal adhesion kinase (FAK) activity and Rho/Rac/Cdc42 protein levels were increased, resulting in migration defects. Using nanonet force microscopy, we determined that cell:extracellular matrix adhesion and cell contractility forces were decreased, confirming the functional relevance of integrin and Rho protein dysregulation. Pharmacological studies showed that inhibition of both FAK1 and proline-rich tyrosine kinase 2 partially restored integrin β1 expression, suggesting negative regulation of integrin β1 by FAK. Together our data indicate that IPMK participates in the regulation of cell migration and provides a potential link between metformin and wound healing impairment.—Tu-Sekine, B., Padhi, A., Jin, S., Kalyan, S., Singh, K., Apperson, M., Kapania, R., Hur, S. C., Nain, A., Kim, S. F. Inositol polyphosphate multikinase is a metformin target that regulates cell migration.

Pipetting Samples

Integrating nanofibers with biochemical gradients to investigate physiologically-relevant fibroblast chemotaxis

September 2, 2019

Persistent cell migration can occur due to anisotropy in the extracellular matrix (ECM), the gradient of a chemo-effector, or a combination of both. Through a variety of in vitro platforms, the contributions of either stimulus have been extensively studied, while the combined effect of both cues remains poorly described. Here, we report an integrative microfluidic chemotaxis assay device that enables the study of single cell chemotaxis on ECM-mimicking, aligned, and suspended nanofibers. Using this assay, we evaluated the effect of fiber spacing on the morphology and chemotaxis response of embryonic murine NIH/3T3 fibroblasts in the presence of temporally invariant, linear gradients of platelet-derived growth factor-BB (PDGF-BB). We found that the strength of PDGF-mediated chemotaxis response depends on not only the gradient slope but also the cell morphology. Low aspect ratio (3.4 ± 0.2) cells on flat substrata exhibited a chemotaxis response only at a PDGF-BB gradient of 0–10 ng mL−1. However, high aspect ratio (19.1 ± 0.7) spindle-shaped cells attached to individual fibers exhibited maximal chemotaxis response at a ten-fold shallower gradient of 0–1 ng mL−1, which was robustly maintained up to 0–10 ng mL−1. Quadrilateral-shaped cells of intermediate aspect ratio (13.6 ± 0.8) attached to two fibers exhibited a weaker response compared to the spindle-shaped cells, but still stronger compared to cells attached to 2D featureless substrata. Through pharmacological inhibition, we show that the mesenchymal chemotaxis pathway is conserved in cells on fibers. Altogether, our findings show that chemotaxis on ECM-mimicking fibers is modulated by fiber spacing-driven cell shape and can be significantly different from the behavior observed on flat 2D substrata. We envisage that this microfluidic platform will have wide applicability in understanding the combined role of ECM architecture and chemotaxis in physiological and pathological processes.

Scientist on Tablet

ECM in Differentiation: A Review of Matrix Structure, Composition and Mechanical Properties

September 4, 2019

Stem cell regenerative potential owing to the capacity to self-renew as well as differentiate into other cell types is a promising avenue in regenerative medicine. Stem cell niche not only provides physical scaffolding but also possess instructional capacity as it provides a milieu of biophysical and biochemical cues. Extracellular matrix (ECM) has been identified as a major dictator of stem cell lineage, thus understanding the structure of in vivo ECM pertaining to specific tissue differentiation will aid in devising in vitro strategies to improve the differentiation efficiency. In this review, we summarize details about the native architecture, composition and mechanical properties of in vivo ECM of the early embryonic stages and the later adult stages. Native ECM from adult tissues categorized on their origin from respective germ layers are discussed while engineering techniques employed to facilitate differentiation of stem cells into particular lineages are noted. Overall, we emphasize that in vitro strategies need to integrate tissue specific ECM biophysical cues for developing accurate artificial environments for optimizing stem cell differentiation.

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Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

june 24, 2019

Biomechanical cues within tissue microenvironments are critical for maintaining homeostasis, and their disruption can contribute to malignant transformation and metastasis. Once transformed, metastatic cancer cells can migrate persistently by adapting (plasticity) to changes in the local fibrous extracellular matrix, and current strategies to recapitulate persistent migration rely exclusively on the use of aligned geometries. Here, the controlled interfiber spacing in suspended Crosshatch networks of nanofibers induces cells to exhibit plasticity in migratory behavior (persistent and random) and the associated cytoskeletal arrangement. At dense spacing (3 and 6 µm), unexpectedly, elongated cells migrate persistently (in 1 dimension) at high speeds in 3‐dimensional shapes with thick nuclei, and short focal adhesion cluster (FAC) lengths. With increased spacing (18 and 36 µm), cells attain 2‐dimensional morphologies, have flattened nuclei and longer FACs, and migrate randomly by rapidly detaching their trailing edges that strain the nuclei by ∼35%. At 54‐µm spacing, kite‐shaped cells become near stationary. Poorly developed filamentous actin stress fibers are found only in cells on 3‐µm networks. Gene‐expression profiling shows a decrease in transcriptional potential and a differential up‐regulation of metabolic pathways. The consistency in observed phenotypes across cell lines supports using this platform to dissect hallmarks of plasticity in migration in vitro .—Jana, A., Nookaew, I., Singh, J., Behkam, B., Franco, A. T., Nain, A. S. Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response.

Embryonic Stem Cells

Design of Fiber Networks for Studying Metastatic Invasion

October 28, 2018

Cancer metastasis, the dissemination of cancer cells from the primary tumor site to distal organs in the body, is one of the leading causes of cancer-related deaths globally. It is now appreciated that metastatic cells take advantage of specific features of surrounding fibrous extracellular matrix that favors invasion. However, the exact contributions of the role of fiber feature size, orientation, and organization remain only partially described. Here using non-electrospinning Spinneret based Tunable Engineered Parameters (STEP) fiber platform, we detail our quantitative findings over the past decade on cancer cell behavior in environments of controlled fiber dimensions, orientation, and hierarchy that can mimic essential features of native ECM. We present a biophysical model of invasion along aligned fibers that starts with cells forming protrusions followed by invasion of cells from a monolayer in single, multi-cell chain and collective modes. Using a mismatch of fiber diameters, we describe a new method to protrutype single protrusions and describe migratory behavior of cells in different shapes. Altogether, control over fiber geometry and network architecture enables the STEP platform to unlock a new paradigm in the interrogation of the fundamental biophysical mechanisms underlying the migratory journey of cells during cancer metastasis.


Cancer Protrusions on a Tightrope: Nanofiber Curvature Contrast Quantitates Single Protrusion Dynamics

January 25, 2017

Cell migration is studied with the traditional focus on protrusion-driven cell body displacement, while less is known on morphodynamics of individual protrusions themselves, especially in fibrous environments mimicking extracellular matrix. Here, using suspended fibers, we report integrative and multiscale abilities to study protrusive behavior independent of cell body migration. By manipulating the diameter of fibers in orthogonal directions, we constrain cell migration along large diameter (2 μm) base fibers, while solely allowing cells to sense, initiate, and mature protrusions on orthogonally deposited high-curvature/low diameter (∼100, 200, and 600 nm) protrusive fibers and low-curvature (∼300 and 600 nm width) protrusive flat ribbons. In doing so, we report a set of morphodynamic metrics that precisely quantitate protrusion dynamics. Protrusion growth and maturation occur by rapid broadening at the base to achieve long lengths, a behavior dramatically influenced by curvature. While flat ribbons universally induce the formation of broad and long protrusions, we quantitatively protrutype protrusive behavior of two highly invasive cancer cell lines and find breast adenocarcinoma (MDA-MB-231) to exhibit sensitivity to fiber curvature higher than that of brain glioblastoma DBTRG-05MG. Furthermore, while actin and microtubules localize within protrusions of all sizes, we quantify protrusion size-driven localization of vimentin and, contrary to current understanding, report that vimentin is not required to form protrusions. Using multiple protrusive fibers, we quantify high coordination between hierarchical branches of individual protrusions and describe how the spatial configuration of multiple protrusions regulates cell migratory state. Finally, we describe protrusion-driven shedding and collection of cytoplasmic debris.


Nanonet Force Microscopy for Measuring Cell Forces

May16, 2016

The influence of physical forces exerted by or felt by cells on cell shape, migration, and cytoskeleton arrangement is now widely acknowledged and hypothesized to occur due to modulation of cellular inside-out forces in response to changes in the external fibrous environment (outside-in). Our previous work using the non-electrospinning Spinneret-based Tunable Engineered Parameters’ suspended fibers has revealed that cells are able to sense and respond to changes in fiber curvature and structural stiffness as evidenced by alterations to focal adhesion cluster lengths. Here, we present the development and application of a suspended nanonet platform for measuring C2C12 mouse myoblast forces attached to fibers of three diameters (250, 400, and 800 nm) representing a wide range of structural stiffness (3–50 nN/μm). The nanonet force microscopy platform measures cell adhesion forces in response to symmetric and asymmetric external perturbation in single and cyclic modes. We find that contractility-based, inside-out forces are evenly distributed at the edges of the cell, and that forces are dependent on fiber structural stiffness. Additionally, external perturbation in symmetric and asymmetric modes biases cell-fiber failure location without affecting the outside-in forces of cell-fiber adhesion. We then extend the platform to measure forces of (1) cell-cell junctions, (2) single cells undergoing cyclic perturbation in the presence of drugs, and (3) cancerous single-cells transitioning from a blebbing to a pseudopodial morphology.

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Nanonet Force Microscopy for Measuring Forces in Single Smooth Muscle Cells of Human Aorta

April 6, 2017

A number of innovative methods exist to measure cell–matrix adhesive forces, but they have yet to accurately describe and quantify the intricate interplay of a cell and its fibrous extracellular matrix (ECM). In cardiovascular pathologies, such as aortic aneurysm, new knowledge on the involvement of cell–matrix forces could lead to elucidation of disease mechanisms. To better understand this dynamics, we measured primary human aortic single smooth muscle cell (SMC) forces using nanonet force microscopy in both inside-out (I-O intrinsic contractility) and outside-in (O-I external perturbation) modes. For SMC populations, we measured the I-O and O-I forces to be 12.9 ± 1.0 and 57.9 ± 2.5 nN, respectively. Exposure of cells to oxidative stress conditions caused a force decrease of 57 and 48% in I-O and O-I modes, respectively, and an increase in migration rate by 2.5-fold. Finally, in O-I mode, we cyclically perturbed cells at constant strain of varying duration to simulate in vivo conditions of the cardiac cycle and found that I-O forces decrease with increasing duration and O-I forces decreased by half at shorter cycle times. Thus our findings highlight the need to study forces exerted and felt by cells simultaneously to comprehensively understand force modulation in cardiovascular disease.

aligned fibers direct collective migrati

Aligned Fibers Direct Collective Cell Migration to Engineer Closing and Nonclosing Wound Gaps

July 26, 2017

Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence–based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell–cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology.

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Role of Suspended Fiber Structural Stiffness and Curvature on Single-Cell Migration, Nucleus Shape, and Focal-Adhesion-Cluster Length

December 2, 2014

It has been shown that cellular migration, persistence, and associated cytoskeletal arrangement are highly dependent on substrate stiffness (modulus: N/m2 and independent of geometry), but little is known on how cells respond to subtle changes in local geometry and structural stiffness (N/m). Here, using fibers of varying diameter (400, 700, and 1200 nm) and length (1 and 2 mm) deposited over hollow substrates, we demonstrate that single mouse C2C12 cells attached to single suspended fibers form spindle morphologies that are sensitive to fiber mechanical properties. Over a wide range of increasing structural stiffness (2 to 100+ mN/m), cells exhibited decreases in migration speed and average nucleus shape index of ∼57% (from 58 to 25 μm/h) and ∼26% (from 0.78 to 0.58), respectively, whereas the average paxillin focal-adhesion-cluster (FAC, formed at poles) length increased by ∼38% (from 8 to 11 μm). Furthermore, the increase in structural stiffness directly correlates with cellular persistence, with 60% of cells moving in the direction of increasing structural stiffness. At similar average structural stiffness (25 ± 5 mN/m), cells put out longer FAC lengths on smaller diameters, suggesting a conservation of FAC area, and also exhibited higher nucleus shape index and migration speeds on larger-diameter fibers. Interestingly, cells were observed to deform fibers locally or globally through forces applied through the FAC sites and cells undergoing mitosis were found to be attached to the FAC sites by single filamentous tethers. These varied reactions have implications in developmental and disease biology models as they describe a strong dependence of cellular behavior on the cell’s immediate mechanistic environment arising from alignment and geometry of fibers.

aligned and suspender fiber force probes

Aligned and suspended fiber force probes for drug testing at single cell resolution

September 29, 2014

The role of physical forces in disease onset and progression is widely accepted and this knowledge presents an alternative route to investigating disease models. Recently, numerous force measurement techniques have been developed to probe single and multi-cell behavior. While these methods have yielded fundamental insights, they are yet unable to capture the fibrous extra-cellular matrix biophysical interactions, involving parameters of curvature, structural stiffness (N m−1), alignment and hierarchy, which have been shown to play key roles in disease and developmental biology. Using a highly aggressive glioma model (DBTRG-05MG), we present a platform technology to quantify single cell force modulation (both inside-out and outside-in) with and without the presence of a cytoskeleton altering drug (cytochalasin D) using suspended and aligned fiber networks (nanonets) beginning to represent the aligned glioma environment. The nanonets fused in crisscross patterns were manufactured using the non-electrospinning spinneret based tunable engineering parameters technique. We demonstrate the ability to measure contractile single cell forces exerted by glioma cells attached to and migrating along the fiber axis (inside-out). This is followed by a study of force response of glioma cells attached to two parallel fibers using a probe deflecting the leading fiber (outside-in). The forces are calculated using beam deflection within the elastic limit. Our data shows that cytochalasin D compromises the spreading area of single glioma cells, eventually decreasing their 'inside-out' contractile forces, and 'outside-in' force response to external strain. Most notably, for the first time, we demonstrate the feasibility of using physiologically relevant aligned fiber networks as ultra-sensitive force (~nanoNewtons) probes for investigating drug response and efficacy in disease models at the single cell resolution.

Suspended micro-nano fiber hierarchical

Suspended Micro/Nanofiber Hierarchical Biological Scaffolds Fabricated Using Non-Electrospinning STEP Technique

October 13, 2014

Extracellular matrix (ECM) is a fibrous natural cell environment, possessing complicated micro- and nanoarchitectures, which provide extracellular signaling cues and influence cell behaviors. Mimicking this three-dimensional microenvironment in vitro is a challenge in developmental and disease biology. Here, suspended multilayer hierarchical nanofiber assemblies (diameter from micrometers to less than 100 nm) with accurately controlled fiber orientation and spacing are demonstrated as biological scaffolds fabricated using the non-electrospinning STEP (Spinneret based Tunable Engineered Parameter) fiber manufacturing technique. Micro/nanofiber arrays were manufactured with high parallelism (relative angles between fibers were maintained less than 6°) and well controlled interfiber spacing (<15%). Using these controls, we demonstrate a bottom up hierarchical assembly of suspended six layer structures of progressively reduced diameters and spacing from several polymer systems. We then demonstrate use of STEP scaffolds to study single and multicell arrangement at high magnifications. Specifically, using double layer divergent (0°–90°) suspended nanofibers assemblies, we show precise quantitative control of cell geometry (change in shape index from 0.15 to 0.57 at similar cell areas), and through design of scaffold porosity (80 × 80 μm2 to 5 × 5 μm2) quadruple the cell attachment density. Furthermore, using unidirectional or crisscross patterns of sparse and dense fiber arrays, we are able to control the cell spread area from ∼400 to ∼700 μm2, while the nucleus shape index increases from 0.75 to 0.99 with cells nearly doubling their focal adhesion cluster lengths (∼15 μm) on widely spaced nanofiber arrays. The platform developed in this study allows a wide parametric investigation of biophysical cues which influence cell behaviors with implications in tissue engineering, developmental biology, and disease biology.

Shape dependent cell migration and focal

Shape-dependent cell migration and focal adhesion organization on suspended and aligned nanofiber scaffolds

April 6, 2013

In the body, cells dynamically respond to chemical and mechanical cues from the extracellular matrix (ECM), yet precise mechanisms by which biophysical parameters (stiffness, topography and alignment) affect cell behavior remain unclear. Here, highly aligned and suspended multilayer polystyrene (PS) nanofiber scaffolds are used to study biophysical influences on focal adhesion complex (FAC) arrangement and associated migration behavior of mouse C2C12 cells arranged in specific shapes: spindle, parallel and polygonal. Furthermore, the role of cytoskeletal-altering drugs including blebbistatin, nocodazole and cytochalasin-D on FAC formation and migratory behavior is investigated. For the first time, this work reports that cells on suspended fiber networks, including cells with administered drugs, elongated along the fiber axes and developed longer (∼ 4×) and more concentrated FAC clusters compared to cells on flat PS control substrates. Additionally, substrate designs which topographically restrict sites of cell attachment and align adhesions were found to promote higher migration speeds (spindle: 52 μm h−1, parallel: 39 μm h−1, polygonal: 25 μm h−1, flat: 32 μm h−1). This work demonstrates that suspended fiber topography-induced concentration of FACs along fiber axes generates increased migration potential as opposed to flat surfaces, which diffuse and randomly orient adhesions.

cell-fiber interaction on aligned and su

Cell-Fiber Interactions on Aligned and Suspended Nanofiber Scaffolds

August 1, 2013

Cells interact with fibrous extracellular matrix (ECM) which exhibits varying degrees of alignment throughout the body. In this review, we highlight cell-aligned fiber interactions using the recently-developed Spinneret-based Tunable Engineered Parameters (STEP) fiber manufacturing technique which creates fibrous scaffolds with precise control on fiber diameter, spacing, orientation, and hierarchy. Through manipulation of each individual parameter, we show that multiple cell types (including cancerous) display unique changes in cell shape, cytoskeletal arrangement, focal adhesion distribution, and migration speed while interacting with the suspended STEP fibers. In addition to single-cell responses, we present our findings on higher-level monolayer formation and wound healing models, stem cell differentiation, and hepatic engineering. These single-cell and population-level studies are conducted in the presence of aligned topographical cues that resemble native ECM. Knowledge gained from such studies will help create more accurate in vitro fibrous scaffolds used for the advancement of tissue engineering, disease treatment, and the development of diagnostic and drug testing platforms.

The mechanistic Influence of aligned nan

The Mechanistic Influence of Aligned Nanofibers on Cell Shape, Migration and Blebbing Dynamics of Glioma Cells.

July 2, 2013

Investigating the mechanistic influence of the tumor microenvironment on cancer cell migration and membrane blebbing is crucial in the understanding and eventual arrest of cancer metastasis. In this study, we investigate the effect of suspended and aligned nanofibers on the glioma cytoskeleton, cell shape, migration and plasma membrane blebbing dynamics using a non-electrospinning fiber-manufacturing platform. Cells attached in repeatable shapes of spindle on single fibers, rectangular on two parallel fibers and polygonal on intersecting fibers. Structural stiffness (N m1 ) of aligned and suspended nanofibers (average diameter: 400 nm, length: 4, 6, and 10 mm) was found to significantly alter the migration speed with higher migration on lower stiffness fibers. For cells attached to fibers and exhibiting blebbing, an increase in cellular spread area resulted in both reduced bleb count and bleb size with an overall increase in cell migration speed. Blebs no longer appeared past a critical cellular spread area of approximately 1400 mm2 . Our results highlighting the influence of the mechanistic environment on the invasion dynamics of glioma cells add to the understanding of how biophysical components influence glioma cell migration and blebbing dynamicsInvestigating the mechanistic influence of the tumor microenvironment on cancer cell migration and membrane blebbing is crucial in the understanding and eventual arrest of cancer metastasis. In this study, we investigate the effect of suspended and aligned nanofibers on the glioma cytoskeleton, cell shape, migration and plasma membrane blebbing dynamics using a non-electrospinning fiber-manufacturing platform. Cells attached in repeatable shapes of spindle on single fibers, rectangular on two parallel fibers and polygonal on intersecting fibers. Structural stiffness (N m1 ) of aligned and suspended nanofibers (average diameter: 400 nm, length: 4, 6, and 10 mm) was found to significantly alter the migration speed with higher migration on lower stiffness fibers. For cells attached to fibers and exhibiting blebbing, an increase in cellular spread area resulted in both reduced bleb count and bleb size with an overall increase in cell migration speed. Blebs no longer appeared past a critical cellular spread area of approximately 1400 mm2 . Our results highlighting the influence of the mechanistic environment on the invasion dynamics of glioma cells add to the understanding of how biophysical components influence glioma cell migration and blebbing dynamics.


Dry Spinning Based Spinneret Based Tunable Engineered Parameters (STEP) Technique for Controlled and Aligned Deposition of Polymeric Nanofibers

August 12, 2009

Polymeric nanofibers are finding increasing number of applications and hold the potential to revolutionize diverse fields such as tissue engineering, smart textiles, sensors, and actuators. Aligning and producing high aspect ratio fiber arrays (length/diameter > 2 000) in the sub‐micron and nanoscale diameters has been challenging due to fragility of polymeric materials, thus making it difficult to deposit them as one dimensional structures functionally interfaced with other systems. Here, we present a pseudo dry spinning technique which allows precise control on fiber diameters and further allows deposition of fiber arrays in aligned configurations. Control on fiber diameters ranging from 50–500 nm and having lengths of several millimeters is achieved by altering the polymeric solution concentration. In the dilute and semi‐dilute unentangled concentration domain droplets or beaded fibers are observed to form. Smooth uniform diameter fibers are observed to form at the onset of semi‐dilute entangled concentration regime. For a given molecular weight, the increase in fiber diameter with increasing solution concentration is attributed to both the increase in the entanglement density and the decrease in the radius of gyration of solvated polymer molecules. Using this technique polymeric fiber arrays in single and multiple layers are demonstrated which can be used towards developing strong textiles, biological scaffolds, and sensor networks.

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