An Easy-to-Fabricate Cell Stretcher Reveals Density-Dependent Mechanical Regulation of Collective Cell Movements in Epithelia

Introduction Mechanical forces regulate many facets of cell and tissue biology. Studying the effects of forces on cells requires real-time observations of single- and multi-cell dynamics in tissue models during controlled external mechanical input. Many of the existing devices used to conduct these studies are costly and complicated to fabricate, which reduces the availability of these devices to many laboratories. Methods We show how to fabricate a simple, low-cost, uniaxial stretching device, with readily available materials and instruments that is compatible with high-resolution time-lapse microscopy of adherent cell monolayers. In addition, we show how to construct a pressure controller that induces a repeatable degree of stretch in monolayers, as well as a custom MATLAB code to quantify individual cell strains. Results As an application note using this device, we show that uniaxial stretch slows down cellular movements in a mammalian epithelial monolayer in a cell density-dependent manner. We demonstrate that the effect on cell movement involves the relocalization of myosin downstream of Rho-associated protein kinase (ROCK). Conclusions This mechanical device provides a platform for broader involvement of engineers and biologists in this important area of cell and tissue biology. We used this device to demonstrate the mechanical regulation of collective cell movements in epithelia.

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

Bone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.