Matrix elasticity regulates mesenchymal stem cell chemotaxis.

Journal of cell science (2018-03-15)
Neha Saxena, Pankaj Mogha, Silalipi Dash, Abhijit Majumder, Sameer Jadhav, Shamik Sen

Efficient homing of human mesenchymal stem cells (hMSCs) is likely to be dictated by a combination of physical and chemical factors present in the microenvironment. However, crosstalk between the physical and chemical cues remains incompletely understood. Here, we address this question by probing the efficiency of epidermal growth factor (EGF)-induced hMSC chemotaxis on substrates of varying stiffness (3, 30 and 600 kPa) inside a polydimethylsiloxane (PDMS) microfluidic device. Chemotactic speed was found to be the sum of a stiffness-dependent component and a chemokine concentration-dependent component. While the stiffness-dependent component scaled inversely with stiffness, the chemotactic component was independent of stiffness. Faster chemotaxis on the softest 3 kPa substrates is attributed to a combination of weaker adhesions and higher protrusion rate. While chemotaxis was mildly sensitive to contractility inhibitors, suppression of chemotaxis upon actin depolymerization demonstrates the role of actin-mediated protrusions in driving chemotaxis. In addition to highlighting the collective influence of physical and chemical cues in chemotactic migration, our results suggest that hMSC homing is more efficient on softer substrates.

Product Number
Product Description

Monoclonal Anti-β-Tubulin antibody produced in mouse, clone TUB 2.1, ascites fluid
Collagen, Type I solution from rat tail, BioReagent, suitable for cell culture, sterile-filtered
Trichlorosilane, 99%
hEGF, EGF, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Monoclonal Anti-Vinculin antibody produced in mouse, clone hVIN-1, ascites fluid
Nocodazole, ≥99% (TLC), powder
Poly(dimethylsiloxane), viscosity 1.0 cSt (25 °C)