Extracellular matrix presentation modulates vascular smooth muscle cell mechanotransduction

Sazonova, Olga V.; Isenberg, Brett C.; Herrmann, Jacob; Lee, Kristen L.; Purwada, Alberto; Valentine, Alex D.; Buczek‐Thomas, Jo Ann; Wong, Joyce Y.; Nugent, Matthew A.

doi:10.1016/j.matbio.2014.11.001

Cited by 79 publications

(82 citation statements)

References 37 publications

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“…To that end, we evaluated the migration of VSMCs on gradient substrates coated with either fibronectin or laminin, matrix proteins that have previously been demonstrated to evoke opposing responses to stiffness changes in smooth muscle cells and drive smooth muscle cells toward different phenotypes (27,(35)(36)(37)(38). This model system was chosen both because of its potential relevance to atherosclerosis and its use in previous studies in our laboratory.…”

Section: Discussion Generation Of Hydrogels With Controlled Gradientsmentioning

confidence: 99%

“…Stiffness mapping experiments have shown that plaque stiffness is spatially heterogeneous, and that these changes can be histologically related to the ECM composition of the plaque (20,25). Given the increasing number of examples for which changes in ECM composition in disease are coupled to changes in mechanical properties of the diseased tissue, there is a need for in vitro experimental systems that allow for systematic exploration of how the cellular response to stiffness gradients is modulated by ECM composition.Recent experimental work has demonstrated that the effect of matrix stiffness on cell behaviors such as differentiation, spreading, and motility is modulated by the composition of the ECM on which the cells are grown (26)(27)(28)(29)(30). Though the role of matrix composition has been investigated on uniformly stiff substrates, previous work investigating the cellular response to mechanical gradients has been limited to substrates coated with a single type of matrix protein, typically collagen or fibronectin (31), and the behavioral response of a given cell type to different matrix compositions has yet to be explored in the same study.…”

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confidence: 99%

“…Recent experimental work has demonstrated that the effect of matrix stiffness on cell behaviors such as differentiation, spreading, and motility is modulated by the composition of the ECM on which the cells are grown (26)(27)(28)(29)(30). Though the role of matrix composition has been investigated on uniformly stiff substrates, previous work investigating the cellular response to mechanical gradients has been limited to substrates coated with a single type of matrix protein, typically collagen or fibronectin (31), and the behavioral response of a given cell type to different matrix compositions has yet to be explored in the same study.…”

mentioning

confidence: 99%

“…Though the role of matrix composition has been investigated on uniformly stiff substrates, previous work investigating the cellular response to mechanical gradients has been limited to substrates coated with a single type of matrix protein, typically collagen or fibronectin (31), and the behavioral response of a given cell type to different matrix compositions has yet to be explored in the same study. Previous work in our laboratory has demonstrated that vascular smooth muscle cell (VSMC) adhesion rate, spread area, cytoskeletal assembly, and focal adhesion signaling undergo opposing responses to substrate stiffness depending on whether they are seeded on fibronectin-or laminin-coated substrates (27), and furthermore that VSMCs will preferentially migrate toward stiffer regions (durotaxis) when exposed to mechanical gradients on fibronectin substrates (14,16). Additionally, there is Significance Many cell types have been observed to migrate toward stiffer regions of mechanical gradients in a process termed durotaxis.…”

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confidence: 99%

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Vascular smooth muscle cell durotaxis depends on extracellular matrix composition

Hartman

Isenberg

Chua

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mechanical compliance has been demonstrated to be a key determinant of cell behavior, directing processes such as spreading, migration, and differentiation. Durotaxis, directional migration from softer to more stiff regions of a substrate, has been observed for a variety of cell types. Recent stiffness mapping experiments have shown that local changes in tissue stiffness in disease are often accompanied by an altered ECM composition in vivo. However, the importance of ECM composition in durotaxis has not yet been explored. To address this question, we have developed and characterized a polyacrylamide hydrogel culture platform featuring highly tunable gradients in mechanical stiffness. This feature, together with the ability to control ECM composition, allows us to isolate the effects of mechanical and biological signals on cell migratory behavior. Using this system, we have tracked vascular smooth muscle cell migration in vitro and quantitatively analyzed differences in cell migration as a function of ECM composition. Our results show that vascular smooth muscle cells undergo durotaxis on mechanical gradients coated with fibronectin but not on those coated with laminin. These findings indicate that the composition of the adhesion ligand is a critical determinant of a cell's migratory response to mechanical gradients.durotaxis | cell migration | extracellular matrix | polyacrylamide C ell migration is essential to numerous biological processes, including development, angiogenesis, wound healing, and cancer metastasis (1-4). The movement of cells in these processes is determined by a complex assessment of environmental cues that include soluble factors, ECM composition, orientation, and stiffness. Numerous experiments have demonstrated that directional cell migration can result from gradients in these environmental cues: for example, chemotaxis (cell migration in response to gradients of soluble signals) and haptotaxis (cell migration in response to gradients of bound ligands) have been established in both in vitro and in vivo experimental systems (5-7). More recently, it has been demonstrated that cells are also capable of directed migration in response to gradients in substrate stiffness, a process termed durotaxis (8). Though there have been limited reports of specifically measured in vivo gradients (9), a number of recent stiffness mapping measurements imply the presence of stiffness gradients in both healthy and diseased tissues spanning a wide range of stiffnesses (10-13). In vitro experiments have demonstrated that directed migration in response to stiffness gradients can be observed in numerous cell types, using various materials as substrates, and across various stiffness levels (8,(14)(15)(16)(17)(18)(19). However, the role of ECM composition in mediating this behavior has not been thoroughly investigated.The interplay between mechanical stiffness and matrix composition in normal and pathological physiology is only now becoming appreciated. Recent studies in which tissue stiffness was mapped by atomic fo...

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Section: Discussion Generation Of Hydrogels With Controlled Gradientsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Vascular smooth muscle cell durotaxis depends on extracellular matrix composition

Hartman

Isenberg

Chua

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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125

110

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“…This structural continuity between SMC and elastic lamina is essential to prevent development of thoracic aortic aneurysms. In addition, ECM exhibits profound effects on SMC phenotypes 38, 39 and induces differential responses to stiffness-induced mechanotransduction 40 . The current study further demonstrated that remodeling of ECM and liberation of cleaved fragment by MMP17 during embryogenesis plays a critical role in establishing and maintenance of the vessel integrity, although the long-term rescue effects of N-OPN and whether Mmp17 −/− aortas with N-OPN overexpression prevents from angiotensin II-induced TAA need to be addressed in future studies.…”

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confidence: 99%

MMP17/MT4-MMP and Thoracic Aortic Aneurysms

Papke

Yamashiro

Yanagisawa³

2015

Circulation Research

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Proinflammation, profibrosis, and arterial aging

2020

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Aging is a major risk factor for the morbidity and mortality of quintessential cardiovascular diseases, such as hypertension and atherosclerosis, mainly due to arterial wall structural and functional adverse remodeling, such as intimal medial thickening (IMT) and stiffening. 1-5 The age-associated increase in collagen deposition within the arterial wall is known as arterial profibrosis; and the age-associated increase in sterile inflammation within the wall is known as arterial proinflammation. Proinflammation and profibrosis are the key molecular and cellular events in age-associated IMT and arterial stiffening. It is widely accepted that proinflammatory endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are mainly responsible for age-associated adverse arterial cellular events; however, the consequence of proinflammation and profibrosis (predisposing collagen deposition) greatly affects the behavior of these cells adversely with a predominant impact on the age-associated arterial stiffening, which is not completely understood. 1-5 Aging increases the proinflammatory molecules angiotensin II (Ang II), milk fat globule-EGF8 (MFG-E8), calpain-1, monocyte chemoattractant protein 1 (MCP-1), non-phagocytic nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and

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Extracellular matrix presentation modulates vascular smooth muscle cell mechanotransduction

Cited by 79 publications

References 37 publications

Vascular smooth muscle cell durotaxis depends on extracellular matrix composition

Vascular smooth muscle cell durotaxis depends on extracellular matrix composition

MMP17/MT4-MMP and Thoracic Aortic Aneurysms

Proinflammation, profibrosis, and arterial aging

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