Abstract
Extracellular matrix (ECM), as a dynamic component of the tissue, influences cell behavior and plays an important role in cell mechanics and tissue homeostasis. Reciprocally, this three-dimensional scaffold is dynamically, structurally and mechanically modified by cells. In the field of biophysics, the independent role of cell and ECM mechanics has been largely investigated; however, there is a lack of experimental data reporting the interdependent interplay between cell and ECM mechanics, measured simultaneously. Here, using Atomic Force Microscopy (AFM) we have characterized five different decellularized matrices diverse in their topography, ECM composition and stiffness and cultured them with normal and pathological fibroblasts (scar and Dupuytren’s). We investigated the change in topography and elasticity of these matrices due to cell seeding, by using AFM peak force imaging and mechanical mapping, respectively. We found normal fibroblasts soften these matrices more than pathological fibroblasts, suggesting that pathological fibroblasts are profoundly influencing tissue stiffening in fibrosis. We detected different ECM composition of decellularized matrices used here influences fibroblast stiffness, thus highlighting that cell mechanics not only depends on ECM stiffness but also on their composition. We used confocal microscopy to assess fibroblasts invasion and found pathological fibroblasts were invading the matrices deeper than normal fibroblasts.
Highlights
The extracellular matrix (ECM) is a structural scaffold made of non-cellular, fibrous and non-fibrous proteins that are able to influence cellular functions, tissue homeostasis and organ development[1]
We show that the Young’s modulus of fibroblasts differs when fibroblasts are seeded on different matrices, possibly due to the peculiar matrix composition, implicating the dependence of cell mechanics to Extracellular matrix (ECM) composition
Atomic Force Microscopy (AFM) measurements were performed on bare matrices, and cells were seeded on the matrices and cultured for two weeks
Summary
The extracellular matrix (ECM) is a structural scaffold made of non-cellular, fibrous and non-fibrous proteins that are able to influence cellular functions, tissue homeostasis and organ development[1]. The ECM microenvironment mediates cell adhesion by providing the anchoring sequence tripeptide Arg-Gly-Asp (RGD) to cell transmembrane anchoring proteins such as integrins, which are an integral part of focal adhesions (FA)[3,4,5] This molecular assembly connects cells and ECM via force pinpoints and contributes to cellular signaling such as mechano-sensation and mechanotransduction[6,7,8]. The tremendous complexity of the 3D microenvironment makes the deep understanding of the mechanical reciprocity between cells and ECM very complicated which in turn results in difficulties to follow the changes in cell and ECM mechanics at the same time To overcome this issue, there is a strong need to employ more complex and heterogeneous matrices able to provide the full range of signals, where cells are exposed to, in near physiological conditions
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