Editing Extracellular matrix (section)

== Function ==
Due to its diverse nature and composition, the ECM can serve many functions, such as providing support, segregating tissues from one another, and regulating intercellular communication. The extracellular matrix regulates a cell's dynamic behavior. In addition, it sequesters a wide range of cellular [[growth factor]]s and acts as a local store for them.<ref name="Robbins"/>  Changes in physiological conditions can trigger [[protease]] activities that cause local release of such stores. This allows the rapid local growth-factor-mediated activation of cellular functions without ''[[De novo synthesis|de novo]]'' synthesis.{{cn|date=April 2025}}

Formation of the extracellular matrix is essential for processes like growth, [[wound healing]], and [[fibrosis]]. An understanding of ECM structure and composition also helps in comprehending the complex dynamics of [[tumor]] invasion and [[metastasis]] in [[Oncology|cancer biology]] as metastasis often involves the destruction of extracellular matrix by enzymes such as [[serine protease]]s, [[threonine protease]]s, and [[matrix metalloproteinase]]s.<ref name="Robbins"/><ref>{{cite journal | vauthors = Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S | s2cid = 4356057 | title = Metastatic potential correlates with enzymatic degradation of basement membrane collagen | journal = Nature | volume = 284 | issue = 5751 | pages = 67–8 | date = March 1980 | pmid = 6243750 | doi = 10.1038/284067a0 | bibcode = 1980Natur.284...67L }}{{Closed access}}</ref>

The [[stiffness]] and [[elasticity (physics)|elasticity]] of the ECM has important implications in [[cell migration]], gene expression,<ref name="WangJHC">{{cite journal | vauthors = Wang JH, Thampatty BP, Lin JS, Im HJ | title = Mechanoregulation of gene expression in fibroblasts | journal = Gene | volume = 391 | issue = 1–2 | pages = 1–15 | date = April 2007 | pmid = 17331678 | pmc = 2893340 | doi = 10.1016/j.gene.2007.01.014 }}{{Closed access}}</ref> and [[Cellular differentiation|differentiation]].<ref name="EnglerAJ">{{cite journal | vauthors = Engler AJ, Sen S, Sweeney HL, Discher DE | s2cid = 16109483 | title = Matrix elasticity directs stem cell lineage specification | journal = Cell | volume = 126 | issue = 4 | pages = 677–89 | date = August 2006 | pmid = 16923388 | doi = 10.1016/j.cell.2006.06.044 | doi-access = free }}{{Closed access}}</ref> Cells actively sense ECM rigidity and migrate preferentially towards stiffer surfaces in a phenomenon called [[durotaxis]].<ref name="LoCM">{{cite journal | vauthors = Lo CM, Wang HB, Dembo M, Wang YL | title = Cell movement is guided by the rigidity of the substrate | journal = Biophysical Journal | volume = 79 | issue = 1 | pages = 144–52 | date = July 2000 | pmid = 10866943 | pmc = 1300921 | doi = 10.1016/S0006-3495(00)76279-5 | bibcode = 2000BpJ....79..144L }}{{Closed access}}</ref> They also detect elasticity and adjust their gene expression accordingly, which has increasingly become a subject of research because of its impact on differentiation and cancer progression.<ref name="ProvenzanoPP">{{cite journal | vauthors = Provenzano PP, Inman DR, Eliceiri KW, Keely PJ | title = Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage | journal = Oncogene | volume = 28 | issue = 49 | pages = 4326–43 | date = December 2009 | pmid = 19826415 | pmc = 2795025 | doi = 10.1038/onc.2009.299 }}{{Closed access}}</ref>

In the brain, [[hyaluronan]] serves as the primary component of the extracellular matrix, contributing to both structural integrity and signaling functions. High-molecular-weight hyaluronan forms a diffusional barrier that regulates local extracellular diffusion. When the ECM undergoes degradation, hyaluronan fragments are released into the extracellular space, where they act as pro-inflammatory molecules, influencing immune cell responses, including those of [[microglia]].<ref name="SoriaFN">{{cite journal | vauthors = Soria FN, Paviolo C, Doudnikoff E, Arotcarena ML, Lee A, Danné N, Mandal AK, Gosset P, Dehay B, Groc L, Cognet L, Bezard E | title = Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling | journal = Nature Communications | volume = 11 | pages = 3440 | date = July 2020 | issue = 1 | pmid = 32651387| doi = 10.1038/s41467-020-17328-9 | pmc = 7351768 | bibcode = 2020NatCo..11.3440S | doi-access = free }}{{Open access}}</ref>

===Cell adhesion===
Many cells bind to components of the extracellular matrix. Cell adhesion can occur in two ways; by [[focal adhesions]], connecting the ECM to [[actin]] filaments of the cell, and [[hemidesmosomes]], connecting the ECM to intermediate filaments such as [[keratin]]. This cell-to-ECM adhesion is regulated by specific cell-surface [[cellular adhesion molecule]]s (CAM) known as [[integrins]]. Integrins are cell-surface proteins that bind cells to ECM structures, such as fibronectin and laminin, and also to integrin proteins on the surface of other cells.{{cn|date=April 2025}}

Fibronectins bind to ECM macromolecules and facilitate their binding to transmembrane integrins. The attachment of fibronectin to the extracellular domain initiates intracellular signalling pathways as well as association with the cellular cytoskeleton via a set of adaptor molecules such as [[actin]].<ref name=ECB/>