Transient mechanical interactions between cells and viscoelastic extracellular matrix

Soft Matter ◽  
2021 ◽  
Author(s):  
Brandon Matthew Slater ◽  
Jing Li ◽  
Dhiraj Indana ◽  
Yihao Xie ◽  
Ovijit Chaudhuri ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Physiological Processes ◽  
Contractile Forces ◽  
Surrounding Extracellular Matrix

During various physiological processes, such as wound healing and cell migration, cells continuously interact mechanically with a surrounding extracellular matrix (ECM). Contractile forces generated by the actin cytoskeleton are transmitted...

Metalloproteinases and their inhibitors in angiogenesis

2003 ◽  
Vol 5 (23) ◽  
pp. 1-39 ◽  
Author(s):  
Marc A. Lafleur ◽  
Madeleine M. Handsley ◽  
Dylan R. Edwards
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Function ◽  
Proteolytic Enzymes ◽  
Biologically Relevant ◽  
Physiological Processes ◽  
Adam Family ◽  
Angiogenic Inhibitors ◽  
Membrane Type

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being crucial for the growth of solid tumours. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9 and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, liberation of angiogenic factors, production of endogenous angiogenic inhibitors, and the unmasking of cryptic biologically relevant sites in ECM components. This review brings together what is currently known about the functions of the MMPs and the closely related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses how this information might be useful in manipulation of the angiogenic process, with a view to controlling aberrant neovascularisation.

scholarly journals Dystroglycan proteolysis is conformationally-regulated and disrupted by disease-associated mutations

2018 ◽  
Author(s):  
Amanda N. Hayward ◽  
Wendy R. Gordon
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Muscular Dystrophy ◽  
Actin Cytoskeleton ◽  
Blood Brain Barrier ◽  
Muscle Cells ◽  
Matrix Metalloproteases ◽  
Neural Cells ◽  
Cellular Phenotype ◽  
Adhesion Receptor

AbstractThe adhesion receptor dystroglycan provides a critical mechanical link between the extracellular matrix (ECM) and the actin cytoskeleton to help muscle cells withstand contraction and neural cells maintain the blood brain barrier. Disrupting the link is associated with diseases such as cancer and muscular dystrophy. Proteolysis of dystroglycan by Matrix Metalloproteases (MMPs) also breaks the mechanical anchor and is amplified in several pathogenic states. We use a combination of biochemical and cell-based assays to show that dystroglycan proteolysis is conformationally regulated by an extracellular, juxtamembrane “proteolysis domain”, comprised of tandem Ig-like and SEA-like domains. The intact proteolysis domain is resistant to MMP cleavage, but structurally-disruptive muscular dystrophy-related mutations sensitize dystroglycan to proteolysis. Moreover, increased dystroglycan proteolysis correlates with faster cell migration, linking proteolysis to a disease-relevant cellular phenotype. Intriguingly, previously uncharacterized cancer-associated mutations that map to the proteolysis domain similarly lead to increases in proteolysis and rates of cell migration, potentially revealing a new pathogenic mechanism in cancer.

Polycaprolactone nanofibers functionalized with placental derived extracellular matrix for stimulating wound healing activity

2018 ◽  
Vol 6 (42) ◽  
pp. 6767-6780 ◽  
Author(s):  
Arun Prabhu Rameshbabu ◽  
Sayanti Datta ◽  
Kamakshi Bankoti ◽  
Elavarasan Subramani ◽  
Koel Chaudhury ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Migration ◽  
Growth Factors ◽  
Inflammatory Responses ◽  
Impaired Wound Healing ◽  
Wound Healing Activity

Impaired wound healing is primarily associated with inadequate angiogenesis, repressed cell migration, deficient synthesis of extracellular matrix (ECM) component/growth factors, and altered inflammatory responses in the wound bed environment.

TGF beta 1 promotes actin cytoskeleton reorganization and migratory phenotype in epithelial tracheal cells in primary culture

1996 ◽  
Vol 109 (9) ◽  
pp. 2207-2219 ◽  
Author(s):  
S. Boland ◽  
E. Boisvieux-Ulrich ◽  
O. Houcine ◽  
A. Baeza-Squiban ◽  
M. Pouchelet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Actin Cytoskeleton ◽  
Primary Culture ◽  
Tgf Beta ◽  
Cytoskeleton Reorganization ◽  
Extracellular Matrix Components ◽  
Migratory Phenotype

In the present study we have investigated the effects of transforming growth factor beta (TGF beta 1) on rabbit tracheal epithelial cells in primary culture, with respect to cell proliferation and differentiation. Epithelial tracheal cells derived from an explant plated on an extracellular matrix, formed an outgrowth resulting from cell division and cell migration. TGF beta 1 treatment produced a negative effect on cell proliferation, but in contrast, promoted a marked enhancement of cell migration and increase in outgrowth surface. TGF beta 1 induced marked cell shape changes, including cell spreading and lack of stratification, associated with reduced cell-cell contacts and increased cell-substratum anchorage, as seen by electron microscopic observations. Immunocytological studies demonstrated major TGF beta 1-induced actin cytoskeleton reorganization, corresponding to the development of a basal stress fiber network and decrease of the annular cell border, without affecting the tight junctions. The migratory phenotype was approached by microcinematography which clearly showed that TGF beta 1 triggered a stimulatory effect on migration of epithelial cells, determined using an image analyzing system. Present findings suggest a beneficial role for TGF beta 1 during wound healing in providing the acquisition of a migratory phenotype, with a higher capacity to migrate either on collagen or on different extracellular matrix components including laminin and fibronectin. Conversely, present data are not consistent with a squamous response to TGF beta 1, since metaplastic differentiation did not occur, as characterized by cytokeratin expression and cross-linked envelopes formation.

The extracellular matrix of lip wounds in fetal, neonatal and adult mice

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 651-668
Author(s):  
D.J. Whitby ◽  
M.W. Ferguson
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Migration ◽  
Inflammatory Response ◽  
Cell Function ◽  
Chondroitin Sulphate ◽  
Scar Formation ◽  
Collagen Types ◽  
Cellular Mechanisms ◽  
Collagen Formation

Wound healing in the fetus occurs rapidly, by a regenerative process and without an inflammatory response, resulting in complete restitution of normal tissue function. By contrast, in the adult, wounds heal with scar formation, which may impair function and inhibit further growth. The cellular mechanisms underlying these differing forms of wound healing are unknown but the extracellular matrix (ECM), through its effects on cell function, may play a key role. We have studied the ECM in upper lip wounds of adult, neonatal and fetal mice at days 14, 16 and 18 of gestation. The spatial and temporal distribution of collagen types I, III, IV, V and VI, fibronectin, tenascin, laminin, chondroitin and heparan sulphates were examined immunohistochemically. Results from the fetal groups were essentially similar whilst there were distinct differences between fetus, neonate and adult. Fibronectin was present at the surface of the wound in all groups at 1 h post-wounding. Tenascin was also present at the wound surface but the time at which it was first present differed between fetus (1 h), neonate (12 h) and adult (24 h). The time of first appearance paralleled the rate of wound healing which was most rapid in the fetus and slowest in the adult. Tenascin inhibits the cell adhesion effect of fibronectin and during development the appearance of tenascin correlates with the initiation of cell migration. During wound healing the appearance of tenascin preceded cell migration and the rapid closure of fetal wounds may be due to the early appearance of tenascin in the wound. Collagen types I, III, IV, V and VI were present in all three wound groups but the timing and pattern of collagen deposition differed, with restoration of the normal collagen pattern in the fetus and a scar pattern in the adult. This confirms that lack of scarring in fetal wounds is due to the organisation of collagen within the wound and not simply lack of collagen formation. The distribution of chondroitin sulphate differed between normal fetal and adult tissues and between fetal and adult wounds. Its presence in the fetal wound may alter collagen fibril formation. No inflammatory response was seen in the fetal wounds. The differences in the ECM of fetal and adult wounds suggests that it may be possible to alter the adult wound so that it heals by a fetal-like process without scar formation, loss of tissue function or restriction of growth.

scholarly journals A cytoskeletal clutch mediates cellular force transmission in a soft, three-dimensional extracellular matrix

2017 ◽  
Vol 28 (14) ◽  
pp. 1959-1974 ◽  
Author(s):  
Leanna M. Owen ◽  
Arjun S. Adhikari ◽  
Mohak Patel ◽  
Peter Grimmer ◽  
Natascha Leijnse ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Dynamic Equilibrium ◽  
Three Dimensional ◽  
Time Lapse ◽  
Dermal Fibroblasts ◽  
Force Transmission ◽  
Ecm Remodeling

The ability of cells to impart forces and deformations on their surroundings underlies cell migration and extracellular matrix (ECM) remodeling and is thus an essential aspect of complex, metazoan life. Previous work has resulted in a refined understanding, commonly termed the molecular clutch model, of how cells adhering to flat surfaces such as a microscope coverslip transmit cytoskeletally generated forces to their surroundings. Comparatively less is known about how cells adhere to and exert forces in soft, three-dimensional (3D), and structurally heterogeneous ECM environments such as occur in vivo. We used time-lapse 3D imaging and quantitative image analysis to determine how the actin cytoskeleton is mechanically coupled to the surrounding matrix for primary dermal fibroblasts embedded in a 3D fibrin matrix. Under these circumstances, the cytoskeletal architecture is dominated by contractile actin bundles attached at their ends to large, stable, integrin-based adhesions. Time-lapse imaging reveals that α-actinin-1 puncta within actomyosin bundles move more quickly than the paxillin-rich adhesion plaques, which in turn move more quickly than the local matrix, an observation reminiscent of the molecular clutch model. However, closer examination did not reveal a continuous rearward flow of the actin cytoskeleton over slower moving adhesions. Instead, we found that a subset of stress fibers continuously elongated at their attachment points to integrin adhesions, providing stable, yet structurally dynamic coupling to the ECM. Analytical modeling and numerical simulation provide a plausible physical explanation for this result and support a picture in which cells respond to the effective stiffness of local matrix attachment points. The resulting dynamic equilibrium can explain how cells maintain stable, contractile connections to discrete points within ECM during cell migration, and provides a plausible means by which fibroblasts contract provisional matrices during wound healing.

scholarly journals Mechanical Interactions between a Cell and an Extracellular Environment Facilitate Durotactic Cell Migration

2018 ◽  
Author(s):  
Abdel-Rahman Hassan ◽  
Thomas Biel ◽  
Taeyoon Kim
Keyword(s):  
Cell Migration ◽  
Computational Models ◽  
Biomechanical Model ◽  
Coarse Grained ◽  
Physiological Processes ◽  
Specific Direction ◽  
A Cell ◽  
Stiffness Profile ◽  
Contractile Forces ◽  
Extracellular Environment

ABSTRACTCell migration is a fundamental process in biological systems, playing an important role for diverse physiological processes. Cells often exhibit directed migration in a specific direction in response to various types of cues. In particular, cells are able to sense the rigidity of surrounding environments and then migrate towards stiffer regions. To understand this mechanosensitive behavior called durotaxis, several computational models have been developed. However, most of the models made phenomenological assumptions to recapitulate durotactic behaviors, significantly limiting insights provided from these studies. In this study, we developed a computational biomechanical model without any phenomenological assumption to illuminate intrinsic mechanisms of durotactic behaviors of cells migrating on a two-dimensional substrate. The model consists of a simplified cell generating contractile forces and a deformable substrate coarse-grained into an irregular triangulated mesh. Using the model, we demonstrated that durotactic behaviors emerge from purely mechanical interactions between the cell and the underlying substrate. We investigated how durotactic migration is regulated by biophysical properties of the substrate, including elasticity, viscosity, and stiffness profile.

The Role of Collagen, Fibronectin, Chondronectin and Laminin in Cell Adhesion

1982 ◽  
Vol 40 ◽  
pp. 102-105
Author(s):  
Hynda K. Kleinman ◽  
George R. Martin
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Blood Cells ◽  
Basement Membranes ◽  
Extracellular Matrices ◽  
Structural Support ◽  
Tissue Organization ◽  
Attachment Proteins ◽  
Surrounding Extracellular Matrix

Most cells other than blood cells interact with extracellular matrices composed of various types of collagens, proteoglycans and a newly described group of glycoproteins termed the attachment proteins. Variations in the composition of the extracellular matrix determine the uniqueness of tissues, such as cartilage, bone, dermis and basement membranes. These matrices have numerous functions, including providing structural support to rigid tissues (cartilage, tooth and bone), regulating the passage of macromolecules (kidney basement membrane), and allowing tissues to stretch (blood vessels and skin). In addition, these matrices have potent influences upon the cells which populate them. The anchorage, growth, differentiation, and motility of the resident cells are all determined by their surrounding extracellular matrix. Such matrices are critically important in embryonic development, tissue organization and wound healing.

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