The Number of Lines a Cell Contacts and Cell Contractility Drive the Efficiency of Contact Guidance

Romsey, Nicholas R.; Rodriguez, Laura Lara; Schneider, Ian C.

doi:10.1007/s12195-013-0299-2

Cited by 10 publications

(25 citation statements)

References 53 publications

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“…In addition to gratings, μCP has been used as a contact guidance cue. The average directionality increases with increased line period [60, 61], spacing [15, 16] and adhesiveness [15, 16]. The directionality of MTLn3 cells in this study matches well with what we have seen previously [15].…”

Section: Discussionsupporting

confidence: 88%

“…The average directionality increases with increased line period [60, 61], spacing [15, 16] and adhesiveness [15, 16]. The directionality of MTLn3 cells in this study matches well with what we have seen previously [15]. When comparing gratings to μCP lines of ECM, others have shown that gratings are less potent than lines at dimensions that approximately match ours [62], whereas larger dimensions show that gratings are more potent [63].…”

Section: Discussionmentioning

confidence: 99%

“…Cell speed and directionality were calculated over a time lag of 2 min averaged over 12 hrs as described in a previous paper [15]. …”

Section: Methodsmentioning

confidence: 99%

“…Most contact guidance work has been carried out on gratings [9-12] that present either micro- or nano- sized grooves and ridges from 50 nm to 50 μm in width with depths ranging from 30 nm to 3 μm. In addition to gratings, lines of extracellular matrix (ECM) have been printed such that cells occupy one line and move randomly in 1D [13, 14] or span several lines [15-18]. Finally, aligned collagen fibrils have been epitaxially grown on mica [19].…”

Section: Introductionmentioning

confidence: 99%

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Myosin phosphorylation on stress fibers predicts contact guidance behavior across diverse breast cancer cells

Wang

Schneider

2017

Biomaterials

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During cancer progression the extracellular matrix is remodeled, forming aligned collagen fibers that proceed radially from the tumor, resulting in invasion. We have recently shown that different invasive breast cancer cells respond to epitaxially grown, aligned collagen fibrils differently. This article develops insight into why these cells differ in their contact guidance fidelity. Small changes in contractility or adhesion dramatically alter directional persistence on aligned collagen fibrils, while migration speed remains constant. The directionality of highly contractile and adhesive MDA-MB-231 cells can be diminished by inhibiting Rho kinase or β1 integrin binding. Inversely, the directionality of less contractile and adhesive MTLn3 cells can be enhanced by activating contractility or integrins. Subtle, but quantifiable alterations in myosin II regulatory light chain phosphorylation on stress fibers explain the tuning of contact guidance fidelity, separate from migration per se indicating that the contractile and adhesive state of the cell in combination with collagen organization in the tumor microenvironment determine the efficiency of migration. Understanding how distinct cells respond to contact guidance cues will not only illuminate mechanisms for cancer invasion, but will also allow for the design of environments to separate specific subpopulations of cells from patient-derived tissues by leveraging differences in responses to directional migration cues.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

“…Cell speed and directionality were calculated over a time lag of 2 min averaged over 12 hrs as described in a previous paper [15]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Myosin phosphorylation on stress fibers predicts contact guidance behavior across diverse breast cancer cells

Wang

Schneider

2017

Biomaterials

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“…1 1/2-22 mm square coverslips (Corning Inc., Corning, New York, USA) were sonicated 30 minutes in the following solutions to make squeaky clean coverslips: hot tap water with Versa Clean detergent (Fisher Scientific, Hampton, New Hampshire, USA), hot tap water, distilled water, double distilled water, 1 mM EDTA solution (Fisher Scientific, Hampton, New Hampshire, USA), 70% ethanol in water and 100% ethanol. An adaptation of a protocol to functionalize coverslips with glutaraldehyde was used [40,41]. Cleaned coverslips were soaked in a 3:1 sulfuric acid (Fisher Scientific, Hampton, New Hampshire, USA):30% hydrogen peroxide (Fisher Scientific, Hampton, New Hampshire, USA) solution for one hour, washed with double distilled water and placed in 10 mL of 1% aminopropyltriethylsilane (APTES) (Fisher Scientific, Hampton, New Hampshire, USA) in 10 mM acetic acid for two hours.…”

Section: Collagen Substrate Treatmentmentioning

confidence: 99%

Collagen attachment to the substrate controls cell clustering through migration

Rodriguez¹,

Wang²,

Schneider³

2014

Phys. Biol.

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Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell-cell junctions. Much less is known about how the ECM regulates cells with weak cell-cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in the clustering, changes in cell motility could. Cells plated under conditions that resulted in more clustering had a lower persistence time and slower migration rate than those under conditions that resulted in less clustering. Understanding how the ECM regulates clustering will not only impact the fundamental understanding of cancer progression, but also will guide the design of tissue engineered constructs that allow for the clustering or dissemination of cells throughout the construct. ABSTRACT:Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell-cell junctions. Much less is known about how the ECM regulates cells with weak cell-cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in the clustering, changes in cell motility could. Cells plated under conditions that resulted in more clustering had a lower persistence time and slower migration rate than those under conditions that resulted in less clustering. Understanding how the ECM regulates clustering will not only impact the fundamental understanding of cancer progression, but also will guide the design of tissue engineered constructs that allow for the clustering or dissemination of cells throughout the construct.This is a manuscript of an article from Physical Biology 11 (2014): 056007,

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Microtissue size and cell-cell communication modulate cell migration in arrayed 3D collagen gels

Nuhn

Gong

Che

et al. 2018

Biomed Microdevices

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Cells communicate through the extracellular matrix (ECM) in many physiological and pathological processes. This is particularly important during cell migration, where cell communication can alter both the speed and the direction of migration. However, most cell culture systems operate with large volumes relative to cell numbers, creating low cell densities and diluting factors that mediate cell communication. Furthermore, they lack the ability to isolate single cells or small groups of cells. Droplet forming devices allow for an ability to embed single or small groups of cells into small volume segregated 3D environments, increasing the cell density to physiological levels. In this paper we show a microfluidic droplet device for fabricating 3D collagen-based microtissues to study breast cancer cell motility. MDA-MB-231 cells fail to spread and divide in small, thin chambers. Cell migration is also stunted as compared to thick 3D gels. However, larger chambers formed by a thicker devices promote cell spreading, cell division and faster migration. In the large devices, both cell-ECM and cell-cell interactions affect cell motility. Increasing collagen density decreases cell migration and increasing the number of cells per chamber increases cell migration speed. Furthermore, cells appear to sense both the ECM-chamber wall interface as well as other cells. Cells migrate towards the ECM-chamber interface if within roughly 150 μm, whereas cells further than 150 μm tend to move towards the center of the chamber. Finally, while cells do not show enhanced movement towards the center of mass of a cell cluster, their migration speed is more variable when further away from the cell cluster center of mass. These results show that microfluidic droplet devices can array 3D collagen gels and promote cell spreading, division and migration similar to what is seen in thick 3D collagen gels. Furthermore, they can provide a new avenue to study cell migration and cell-cell communication at physiologically relevant cell densities.

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The Number of Lines a Cell Contacts and Cell Contractility Drive the Efficiency of Contact Guidance

Cited by 10 publications

References 53 publications

Myosin phosphorylation on stress fibers predicts contact guidance behavior across diverse breast cancer cells

Myosin phosphorylation on stress fibers predicts contact guidance behavior across diverse breast cancer cells

Collagen attachment to the substrate controls cell clustering through migration

Microtissue size and cell-cell communication modulate cell migration in arrayed 3D collagen gels

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