000046553 001__ 46553
000046553 005__ 20210121114530.0
000046553 0247_ $$2doi$$a10.1371/journal.pone.0124529
000046553 0248_ $$2sideral$$a89490
000046553 037__ $$aART-2015-89490
000046553 041__ $$aeng
000046553 100__ $$0(orcid)0000-0003-0509-1450$$aMousavi, Seyed Jamaleddin$$uUniversidad de Zaragoza
000046553 245__ $$aRole of Mechanical Cues in Cell Differentiation and Proliferation: A 3D Numerical Model
000046553 260__ $$c2015
000046553 5060_ $$aAccess copy available to the general public$$fUnrestricted
000046553 5203_ $$aCell differentiation, proliferation and migration are essential processes in tissue regenera- tion. Experimental evidence confirms that cell differentiation or proliferation can be regulat- ed according to the extracellular matrix stiffness. For instance, mesenchymal stem cells (MSCs) can differentiate to neuroblast, chondrocyte or osteoblast within matrices mimicking the stiffness of their native substrate. However, the precise mechanisms by which the sub- strate stiffness governs cell differentiation or proliferation are not well known. Therefore, a mechano-sensing computational model is here developed to elucidate how substrate stiff- ness regulates cell differentiation and/or proliferation during cell migration. In agreement with experimental observations, it is assumed that internal deformation of the cell (a me- chanical signal) together with the cell maturation state directly coordinates cell differentia- tion and/or proliferation. Our findings indicate that MSC differentiation to neurogenic, chondrogenic or osteogenic lineage specifications occurs within soft (0.1-1 kPa), intermedi- ate (20-25 kPa) or hard (30-45 kPa) substrates, respectively. These results are consistent with well-known experimental observations. Remarkably, when a MSC differentiate to a compatible phenotype, the average net traction force depends on the substrate stiffness in such a way that it might increase in intermediate and hard substrates but it would reduce in a soft matrix. However, in all cases the average net traction force considerably increases at the instant of cell proliferation because of cell-cell interaction. Moreover cell differentiation and proliferation accelerate with increasing substrate stiffness due to the decrease in the cell maturation time. Thus, the model provides insights to explain the hypothesis that sub- strate stiffness plays a key role in regulating cell fate during mechanotaxis.
000046553 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/MAT2013-46467-C4-3-R
000046553 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000046553 590__ $$a3.057$$b2015
000046553 591__ $$aMULTIDISCIPLINARY SCIENCES$$b11 / 62 = 0.177$$c2015$$dQ1$$eT1
000046553 592__ $$a1.427$$b2015
000046553 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2015$$dQ1
000046553 593__ $$aMedicine (miscellaneous)$$c2015$$dQ1
000046553 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000046553 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000046553 700__ $$0(orcid)0000-0003-0088-7222$$aHamdy Doweidar, Mohamed$$uUniversidad de Zaragoza
000046553 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000046553 773__ $$g10, 5 (2015), e0124529 [23 pp$$pPLoS One$$tPloS one$$x1932-6203
000046553 8564_ $$s724154$$uhttps://zaguan.unizar.es/record/46553/files/texto_completo.pdf$$yVersión publicada
000046553 8564_ $$s102930$$uhttps://zaguan.unizar.es/record/46553/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000046553 909CO $$ooai:zaguan.unizar.es:46553$$particulos$$pdriver
000046553 951__ $$a2021-01-21-11:09:46
000046553 980__ $$aARTICLE