Techniques for assessing 3-D cell–matrix mechanical interactions in vitro and in vivo

Abstract

Cellular interactions with extracellular matrices (ECM) through the application of mechanical forces mediate numerous biological processes including developmental morphogenesis, wound healing and cancer metastasis. They also play a key role in the cellular repopulation and/or remodeling of engineered tissues and organs. While 2-D studies can provide important insights into many aspects of cellular mechanobiology, cells reside within 3-D ECMs in vivo, and matrix structure and dimensionality have been shown to impact cell morphology, protein organization and mechanical behavior. Global measurements of cell-induced compaction of 3-D collagen matrices can provide important insights into the regulation of overall cell contractility by various cytokines and signaling pathways. However, to understand how the mechanics of cell spreading, migration, contraction and matrix remodeling are regulated at the molecular level, these processes must also be studied in individual cells. Here we review the evolution and application of techniques for imaging and assessing local cell-matrix mechanical interactions in 3-D culture models, tissue explants and living animals.

Assessment of Corneal Stromal Remodeling and Regeneration after Photorefractive Keratectomy

“…We also observed punctate F-actin labeling that co-aligned with collagen in both the remodeling and regenerative regions, which is a hallmark of cell-matrix mechanical interactions 27 , 74 , 75 . Cell contractility has been shown to influence non-cell-derived collagen patterning based on forces imposed on the local ECM environment in in vitro studies 76 – 78 .…”

Analysis of multiple types of human cells subsequent to bioprinting with electrospraying technology

“…Besides, mammalian cells strongly depend on the culture conditions and are much more sensitive to heat and mechanical stress (15). In addition, the cell numbers and types, spatial arrangement of cells, and interaction between the cells and the extracellular microenvironment in a 3D structure remain largely intractable, which affects the cell morphology, mechanical behavior and adhesion ability more than planar substrates (10,22). Thus, building human tissue analogues in the reconstructed microenvironment remains a challenge.…”

Computational Modelling of Cancer Development and Growth: Modelling at Multiple Scales and Multiscale Modelling

“…Details of the implementation can be found in Szymańska (2014, 2015b,a). Adopting this approach, we model each cell as an isotropic elastic object capable of migration and division and parameterise it by cell-kinetic, biophysical and cell-biological parameters that can be experimentally measured, from both in vitro and in vivo experiments (Chu et al, 2004;Gumbiner, 2005;Jagiella et al, 2016;Miron-Mendoza et al, 2013;Näthke et al, 1995;Schlüter et al, 2012Schlüter et al, , 2015Ritchie et al, 2001;Zaman et al, 2006). We assume that an individual cell c i in isolation is spherical and characterise the cell shape by its radius R. The position of the cell in 3D space is described by the Cartesian coordinates (x ci , y ci , z ci ) of its centre.…”