Cell Morphology and Focal Adhesion Location Alters Internal Cell Stress

Overview

Journal J R Soc Interface

Specialties Biology
Biomedical Engineering
Biophysics

Date 2014 Oct 10

PMID 25297316

Citations 22

Authors

C A Mullen

T J Vaughan

M C Voisin

M A Brennan

P Layrolle

L M McNamara

Affiliations

Soon will be listed here.

Abstract

Extracellular mechanical cues have been shown to have a profound effect on osteogenic cell behaviour. However, it is not known precisely how these cues alter intracellular mechanics to initiate changes in cell behaviour. In this study, a combination of in vitro culture of MC3T3-E1 cells and finite-element modelling was used to investigate the effects of passive differences in substrate stiffness on intracellular mechanics. Cells on collagen-based substrates were classified based on the presence of cell processes and the dimensions of various cellular features were quantified. Focal adhesion (FA) density was quantified from immunohistochemical staining, while cell and substrate stiffnesses were measured using a live-cell atomic force microscope. Computational models of cell morphologies were developed using an applied contraction of the cell body to simulate active cell contraction. The results showed that FA density is directly related to cell morphology, while the effect of substrate stiffness on internal cell tension was modulated by both cell morphology and FA density, as investigated by varying the number of adhesion sites present in each morphological model. We propose that the cells desire to achieve a homeostatic stress state may play a role in osteogenic cell differentiation in response to extracellular mechanical cues.

Citing Articles

Impact of ionizing radiation on cell-ECM mechanical crosstalk in breast cancer.

Mottareale R, Frascogna C, La Verde G, Arrichiello C, Muto P, Netti P Front Bioeng Biotechnol. 2024; 12:1408789.

PMID: 38903185 PMC: 11187264. DOI: 10.3389/fbioe.2024.1408789.

The actin-bundling protein, PLS3, is part of the mechanoresponsive machinery that regulates osteoblast mineralization.

Chin S, Unnold-Cofre C, Naismith T, Jansen S Front Cell Dev Biol. 2023; 11:1141738.

PMID: 38089885 PMC: 10711096. DOI: 10.3389/fcell.2023.1141738.

Differences and similarities in biophysical and biological characteristics between U87 MG glioblastoma and astrocyte cells.

Ozdil B, Calik-Kocaturk D, Altunayar-Unsalan C, Acikgoz E, Oltulu F, Gorgulu V Histochem Cell Biol. 2023; 161(1):43-57.

PMID: 37700206 DOI: 10.1007/s00418-023-02234-0.

Chitosan-Silica Hybrid Biomaterials for Bone Tissue Engineering: A Comparative Study of Xerogels and Aerogels.

Perez-Moreno A, Pinero M, Fernandez-Montesinos R, Pinaglia-Tobaruela G, Reyes-Peces M, Mesa-Diaz M Gels. 2023; 9(5).

PMID: 37232975 PMC: 10217634. DOI: 10.3390/gels9050383.

A possible molecular mechanism for mechanotransduction at cellular focal adhesion complexes.

Kim J Biophys Rep (N Y). 2022; 1(1):100006.

PMID: 36425310 PMC: 9680735. DOI: 10.1016/j.bpr.2021.100006.

References

Dallas S, Bonewald L . Dynamics of the transition from osteoblast to osteocyte. Ann N Y Acad Sci. 2010; 1192:437-43. PMC: 2981593. DOI: 10.1111/j.1749-6632.2009.05246.x. View

Domke , Dannohl , Parak , Muller , Aicher , Radmacher . Substrate dependent differences in morphology and elasticity of living osteoblasts investigated by atomic force microscopy. Colloids Surf B Biointerfaces. 2000; 19(4):367-379. DOI: 10.1016/s0927-7765(00)00145-4. View

Sit S, Manser E . Rho GTPases and their role in organizing the actin cytoskeleton. J Cell Sci. 2011; 124(Pt 5):679-83. DOI: 10.1242/jcs.064964. View

Mullen C, Haugh M, Schaffler M, Majeska R, McNamara L . Osteocyte differentiation is regulated by extracellular matrix stiffness and intercellular separation. J Mech Behav Biomed Mater. 2013; 28:183-94. PMC: 5776008. DOI: 10.1016/j.jmbbm.2013.06.013. View

Sato H, Kataoka N, Kajiya F, Katano M, Takigawa T, Masuda T . Kinetic study on the elastic change of vascular endothelial cells on collagen matrices by atomic force microscopy. Colloids Surf B Biointerfaces. 2004; 34(2):141-6. DOI: 10.1016/j.colsurfb.2003.12.013. View

Bian L, Hou C, Tous E, Rai R, Mauck R, Burdick J . The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy. Biomaterials. 2012; 34(2):413-21. PMC: 3578381. DOI: 10.1016/j.biomaterials.2012.09.052. View

Discher D, Janmey P, Wang Y . Tissue cells feel and respond to the stiffness of their substrate. Science. 2005; 310(5751):1139-43. DOI: 10.1126/science.1116995. View

Bonewald L . Mechanosensation and Transduction in Osteocytes. Bonekey Osteovision. 2007; 3(10):7-15. PMC: 1847717. DOI: 10.1138/20060233. View

Ducy P, Zhang R, Geoffroy V, Ridall A, Karsenty G . Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89(5):747-54. DOI: 10.1016/s0092-8674(00)80257-3. View

10.

McBeath R, Pirone D, Nelson C, Bhadriraju K, Chen C . Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004; 6(4):483-95. DOI: 10.1016/s1534-5807(04)00075-9. View

11.

Galbraith C, Sheetz M . Forces on adhesive contacts affect cell function. Curr Opin Cell Biol. 1998; 10(5):566-71. DOI: 10.1016/s0955-0674(98)80030-6. View

12.

Caille N, Thoumine O, Tardy Y, Meister J . Contribution of the nucleus to the mechanical properties of endothelial cells. J Biomech. 2002; 35(2):177-87. DOI: 10.1016/s0021-9290(01)00201-9. View

13.

Dailey H, Ricles L, Yalcin H, Ghadiali S . Image-based finite element modeling of alveolar epithelial cell injury during airway reopening. J Appl Physiol (1985). 2008; 106(1):221-32. DOI: 10.1152/japplphysiol.90688.2008. View

14.

Egerbacher M, Arnoczky S, Caballero O, Lavagnino M, Gardner K . Loss of homeostatic tension induces apoptosis in tendon cells: an in vitro study. Clin Orthop Relat Res. 2008; 466(7):1562-8. PMC: 2505255. DOI: 10.1007/s11999-008-0274-8. View

15.

Peck J, Oberst M, Bouker K, Bowden E, Burbelo P . The RhoA-binding protein, rhophilin-2, regulates actin cytoskeleton organization. J Biol Chem. 2002; 277(46):43924-32. DOI: 10.1074/jbc.M203569200. View

16.

Quarles L, Yohay D, Lever L, Caton R, Wenstrup R . Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J Bone Miner Res. 1992; 7(6):683-92. DOI: 10.1002/jbmr.5650070613. View

17.

Mizutani T, Haga H, Kawabata K . Cellular stiffness response to external deformation: tensional homeostasis in a single fibroblast. Cell Motil Cytoskeleton. 2004; 59(4):242-8. DOI: 10.1002/cm.20037. View

18.

Vogel V, Sheetz M . Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol. 2006; 7(4):265-75. DOI: 10.1038/nrm1890. View

19.

Ponik S, Pavalko F . Formation of focal adhesions on fibronectin promotes fluid shear stress induction of COX-2 and PGE2 release in MC3T3-E1 osteoblasts. J Appl Physiol (1985). 2004; 97(1):135-42. DOI: 10.1152/japplphysiol.01260.2003. View

20.

Kuznetsova T, Starodubtseva M, Yegorenkov N, Chizhik S, Zhdanov R . Atomic force microscopy probing of cell elasticity. Micron. 2007; 38(8):824-33. DOI: 10.1016/j.micron.2007.06.011. View