Editing Extracellular matrix (section)

===Stiffness and elasticity===
The ECM can exist in varying degrees of [[stiffness]] and [[elasticity (physics)|elasticity]], from soft brain tissues to hard bone tissues. The elasticity of the ECM can differ by several orders of magnitude. This property is primarily dependent on [[collagen]] and [[elastin]] concentrations,<ref name=bonnans/> and it has recently been shown to play an influential role in regulating numerous cell functions.

Cells can sense the mechanical properties of their environment by applying forces and measuring the resulting backlash.<ref name="PlotnikovSV">{{cite journal | vauthors = Plotnikov SV, Pasapera AM, Sabass B, Waterman CM | title = Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration | journal = Cell | volume = 151 | issue = 7 | pages = 1513–27 | date = December 2012 | pmid = 23260139 | pmc = 3821979 | doi = 10.1016/j.cell.2012.11.034 }}{{Closed access}}</ref>  This plays an important role because it helps regulate many important cellular processes including cellular contraction,<ref name="DischerDE">{{cite journal | vauthors = Discher DE, Janmey P, Wang YL | title = Tissue cells feel and respond to the stiffness of their substrate | journal = Science | volume = 310 | issue = 5751 | pages = 1139–43 | date = November 2005 | pmid = 16293750 | doi = 10.1126/science.1116995 | citeseerx = 10.1.1.318.690 | bibcode = 2005Sci...310.1139D | s2cid = 9036803 }}{{Closed access}}</ref> [[cell migration]],<ref name="LoCM"/> [[cell proliferation]],<ref>{{cite journal | vauthors = Hadjipanayi E, Mudera V, Brown RA | title = Close dependence of fibroblast proliferation on collagen scaffold matrix stiffness | journal = Journal of Tissue Engineering and Regenerative Medicine | volume = 3 | issue = 2 | pages = 77–84 | date = February 2009 | pmid = 19051218 | doi = 10.1002/term.136 | s2cid = 174311 | doi-access = free }}{{Closed access}}</ref> [[Cellular differentiation|differentiation]]<ref name="EnglerAJ"/> and cell death ([[apoptosis]]).<ref name="WangHB">{{cite journal | vauthors = Wang HB, Dembo M, Wang YL | title = Substrate flexibility regulates growth and apoptosis of normal but not transformed cells | journal = American Journal of Physiology. Cell Physiology | volume = 279 | issue = 5 | pages = C1345-50 | date = November 2000 | pmid = 11029281 | doi = 10.1152/ajpcell.2000.279.5.C1345 }}{{Closed access}}</ref>
Inhibition of nonmuscle [[myosin II]] blocks most of these effects,<ref name="EnglerAJ"/><ref name="LoCM"/><ref name="DischerDE"/> indicating that they are indeed tied to sensing the mechanical properties of the ECM, which has become a new focus in research during the past decade.

====Effect on gene expression====
Differing mechanical properties in ECM exert effects on both cell behaviour and [[gene expression]].<ref>{{cite journal |last1=Wahbi |first1=Wafa |last2=Naakka |first2=Erika |last3=Tuomainen |first3=Katja |last4=Suleymanova |first4=Ilida |last5=Arpalahti |first5=Annamari |last6=Miinalainen |first6=Ilkka |last7=Vaananen |first7=Juho |last8=Grenman |first8=Reidar |last9=Monni |first9=Outi |last10=Al-Samadi |first10=Ahmed |last11=Salo |first11=Tuula |title=The critical effects of matrices on cultured carcinoma cells: Human tumor-derived matrix promotes cell invasive properties |journal=Experimental Cell Research |date=February 2020 |volume=389 |issue=1 |pages=111885 |doi=10.1016/j.yexcr.2020.111885 |pmid=32017929 |hdl=10138/325579 |s2cid=211035510 |url=http://urn.fi/urn:nbn:fi-fe2020051435636 |hdl-access=free }}</ref> Although the mechanism by which this is done has not been thoroughly explained, [[Hemidesmosome|adhesion complexes]] and the [[actin]]-[[myosin]] [[cytoskeleton]], whose contractile forces are transmitted through transcellular structures are thought to play key roles in the yet to be discovered molecular pathways.<ref name="DischerDE"/>

====Effect on differentiation====
ECM elasticity can direct [[cellular differentiation]], the process by which a cell changes from one cell type to another. In particular, naive [[mesenchymal stem cells]] (MSCs) have been shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. MSCs placed on soft matrices that mimic the brain differentiate into [[neuron]]-like cells, showing similar shape, [[RNAi]] profiles, cytoskeletal markers, and [[transcription factor]] levels. Similarly stiffer matrices that mimic muscle are myogenic, and matrices with stiffnesses that mimic collagenous bone are osteogenic.<ref name="EnglerAJ"/>

====Durotaxis====
{{Main|Durotaxis}}
Stiffness and elasticity also guide [[cell migration]], this process is called [[durotaxis]]. The term was coined by Lo CM and colleagues when they discovered the tendency of single cells to migrate up rigidity gradients (towards more stiff substrates)<ref name="LoCM"/> and has been extensively studied since. The molecular mechanisms behind [[durotaxis]] are thought to exist primarily in the [[focal adhesion]], a large [[protein complex]] that acts as the primary site of contact between the cell and the ECM.<ref>{{cite journal | vauthors = Allen JL, Cooke ME, Alliston T | title = ECM stiffness primes the TGFβ pathway to promote chondrocyte differentiation | journal = Molecular Biology of the Cell | volume = 23 | issue = 18 | pages = 3731–42 | date = September 2012 | pmid = 22833566 | pmc = 3442419 | doi = 10.1091/mbc.E12-03-0172 }}</ref> This complex contains many proteins that are essential to durotaxis including structural anchoring proteins ([[integrins]]) and signaling proteins (adhesion kinase ([[PTK2|FAK]]), [[talin protein|talin]], [[vinculin]], [[paxillin]], [[α-actinin]], [[GTPases]] etc.) which cause changes in cell shape and actomyosin contractility.<ref>{{cite journal | vauthors = Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, Hess HF, Waterman CM | title = Nanoscale architecture of integrin-based cell adhesions | journal = Nature | volume = 468 | issue = 7323 | pages = 580–4 | date = November 2010 | pmid = 21107430 | pmc = 3046339 | doi = 10.1038/nature09621 | bibcode = 2010Natur.468..580K }}</ref> These changes are thought to cause [[cytoskeleton|cytoskeletal]] rearrangements in order to facilitate directional [[cell migration|migration]].{{cn|date=April 2025}}