Subcellular spatial segregation of integrin subtypes by patterned multicomponent surfaces

Desai, Ravi A.; Khan, Muhammad Nadeem; Gopal, Smitha B.; Chen, Christopher

doi:10.1039/c0ib00129e

Cited by 57 publications

(72 citation statements)

References 79 publications

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“…Cell-matrix adhesions are well known to direct cytoskeletal structure [41][42][43][44][45] and can trigger polarity signals via activation of Cdc42 and actin polymerization [46 -48]. In contrast to the repulsive effects of cell -cell adhesions, cell -matrix adhesions appear to attract cell polarity via a process that could be called 'adhesion promotion of locomotion' (APL).…”

Section: Discussionmentioning

confidence: 99%

Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

Desai

Gopal

Chen

et al. 2013

J. R. Soc. Interface.

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123

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Contact inhibition of locomotion (CIL) is the process whereby cells collide, cease migrating in the direction of the collision, and repolarize their migration machinery away from the collision. Quantitative analysis of CIL has remained elusive because cell-to-cell collisions are infrequent in traditional cell culture. Moreover, whereas CIL predicts mutual cell repulsion and 'scattering' of cells, the same cells in vivo are observed to undergo CIL at some developmental times and collective cell migration at others. It remains unclear whether CIL is simply absent during collective cell migration, or if the two processes coexist and are perhaps even related. Here, we used micropatterned stripes of extracellular matrix to restrict cell migration to linear paths such that cells polarized in one of two directions and collisions between cells occurred frequently and consistently, permitting quantitative and unbiased analysis of CIL. Observing repolarization events in different contexts, including headto-head collision, head-to-tail collision, collision with an inert barrier, or no collision, and describing polarization as a two-state transition indicated that CIL occurs probabilistically, and most strongly upon head-to-head collisions. In addition to strong CIL, we also observed 'trains' of cells moving collectively with high persistence that appeared to emerge from single cells. To reconcile these seemingly conflicting observations of CIL and collective cell migration, we constructed an agent-based model to simulate our experiments. Our model quantitatively predicted the emergence of collective migration, and demonstrated the sensitivity of such emergence to the probability of CIL. Thus CIL and collective migration can coexist, and in fact a shift in CIL probabilities may underlie transitions between solitary cell migration and collective cell migration. Taken together, our data demonstrate the emergence of persistently polarized, collective cell movement arising from CIL between colliding cells.

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Section: Discussionmentioning

confidence: 99%

Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

Desai

Gopal

Chen

et al. 2013

J. R. Soc. Interface.

Self Cite

123

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“…Flat or rounded MSC morphologies are associated with osteogenesis or adipogenesis, respectively [13], similar to observations resulting from substrate rigidity variation [11]. To increase experimental throughput and permit combinatorial testing of substrate properties, various geometries, rigidities and biochemical compositions are patterned in high-density arrays using methods such as blotting and microcontact-or screen-printing [13,72,77,78]. By patterning individual ECM components on hydrogel substrates, ECM biochemistry and substrate rigidity interact to guide MSC lineage specification [79].…”

Section: Mechanobiology In Two Dimensionsmentioning

confidence: 99%

“…Cell culture substrate properties are excellent experimental variables that provide key insights into MSC mechanobiology. Historically, these have been achieved by varying substrate elasticity [69][70][71] or adhesive properties that direct cell shape (figure 2b) [13,15,72]; both methods are well suited for miniaturized array-based HTS platforms. Dynamic mechanical loading (figure 2c) is often more challenging to implement than mechanically static cultures but is nevertheless increasingly represented in microfabricated platforms [59,[73][74][75][76].…”

Section: Emerging Experimental Platforms For Multipotent Mesenchymal mentioning

confidence: 99%

Mesenchymal stem cell mechanobiology and emerging experimental platforms

MacQueen

Sun

Simmons

2013

J. R. Soc. Interface.

127

103

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Experimental control over progenitor cell lineage specification can be achieved by modulating properties of the cell's microenvironment. These include physical properties of the cell adhesion substrate, such as rigidity, topography and deformation owing to dynamic mechanical forces. Multipotent mesenchymal stem cells (MSCs) generate contractile forces to sense and remodel their extracellular microenvironments and thereby obtain information that directs broad aspects of MSC function, including lineage specification. Various physical factors are important regulators of MSC function, but improved understanding of MSC mechanobiology requires novel experimental platforms. Engineers are bridging this gap by developing tools to control mechanical factors with improved precision and throughput, thereby enabling biological investigation of mechanics-driven MSC function. In this review, we introduce MSC mechanobiology and review emerging cell culture platforms that enable new insights into mechanobiological control of MSCs. Our main goals are to provide engineers and microtechnology developers with an up-to-date description of MSC mechanobiology that is relevant to the design of experimental platforms and to introduce biologists to these emerging platforms.

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“…Microcontact printing in general is an effective way by which to direct cell migration (Kushiro et al, 2010). Microcontact printing adhesive lines has been used to examine cytoskeleton structure or dynamics (Csucs et al, 2007;Pouthas et al, 2008;Rossier et al, 2010), cell alignment and bridging across lines (Clark et al, 1992;Csucs et al, 2007;Desai et al, 2011;Doyle et al, 2009;Oneill et al, 1990;Rossier et al, 2010), traction forces (Borghi et al, 2010;Rossier et al, 2010) and cell migration (Borghi et al, 2010;Csucs et al, 2007;Doyle et al, 2009;Kandere-Grzybowska et al, 2007;Maiuri et al, 2012 These reports did not fully address how line spacing, non-specific adhesion strength between lines and intracellular contractility impact directed cell migration. The speed of random migration is known to depend on cell contractility.…”

Section: Introductionmentioning

confidence: 99%

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

2013

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Cell migration is an important biological function that impacts many physiological and pathological processes. Often migration is directed along various densities of aligned fibers of collagen, a process called contact guidance. However, cells adhere to other components in the extracellular matrix, possibly affecting migrational behavior. Additionally, changes in intracellular contractility are well known to affect random migration, but its effect on contact guidance is less known. This study examines differences in directed migration in response to variations in the spacing of collagen, non-specific background adhesion strength and myosin II-mediated contractility. Collagen was microcontact printed onto glass substrates and timelapse livecell microscopy was used to measure migration characteristics. Increasing the number of lines a cell contacts or decreasing contraction led to decreases in directionality, but speed changes were context dependent. This suggests that while cell migration speed is a biphasic function of contractility, directionality appears to be a monotonic, increasing function of contractility. Thus, increasing the number of lines a cell contacts or decreasing contractility degrades the contact guidance fidelity. Abstract:Cell migration is an important biological function that impacts many physiological and pathological processes. Often migration is directed along various densities of aligned fibers of collagen, a process called contact guidance. However, cells adhere to other components in the extracellular matrix, possibly affecting migrational behavior. Additionally, changes in intracellular contractility are well known to affect random migration, but its effect on contact guidance is less known. This study examines differences in directed migration in response to variations in the spacing of collagen, non-specific background adhesion strength and myosin II-mediated contractility. Collagen was microcontact printed

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Subcellular spatial segregation of integrin subtypes by patterned multicomponent surfaces

Cited by 57 publications

References 79 publications

Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

Contact inhibition of locomotion probabilities drive solitary versus collective cell migration

Mesenchymal stem cell mechanobiology and emerging experimental platforms

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

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