Discriminating the Independent Influence of Cell Adhesion and Spreading Area on Stem Cell Fate Determination Using Micropatterned Surfaces

Abstract

Adhesion and spreading are essential processes of anchorage dependent cells involved in regulation of cell functions. Cells interact with their extracellular matrix (ECM) resulting in different degree of adhesion and spreading. However, it is not clear whether cell adhesion or cell spreading is more important for cell functions. In this study, 10 types of isotropical micropatterns that were composed of 2 μm microdots were prepared to precisely control the adhesion area and spreading area of human mesenchymal stem cells (MSCs). The respective influence of adhesion and spreading areas on stem cell functions was investigated. Adhesion area showed more significant influences on the focal adhesion formation, binding of myosin to actin fibers, cytoskeletal organization, cellular Young’s modulus, accumulation of YAP/TAZ in nuclei, osteogenic and adipogenic differentiation of MSCs than did the spreading area. The results indicated that adhesion area rather than spreading area played more important roles in regulating cell functions. This study should provide new insight of the influence of cell adhesion and spreading on cell functions and inspire the design of biomaterials to process in an effective manner for manipulation of cell functions.

Actin cytoskeleton self-organization in single epithelial cells and fibroblasts under isotropic confinement

“…Indeed multinucleated cells plated on planar substrates always have larger cell projected areas than their mononucleated counterparts 31 . The interrelationship between the cell projected area and organization of the actin cytoskeleton, development of traction forces and assembly of focal adhesions was observed in many prior studies [18][19][20][32][33][34] . Therefore, the optimal development of the actin cytoskeleton requires a sufficient spreading area that could be different for different cell types.…”

“…A number of studies have found that geometry and size of adhesive islands determine a variety of different aspects of cellular organization and function [16][17][18][19][20] . Therefore, in search of external factors that may determine the self-organization of the actin cytoskeleton we first investigated the effect of a basic scaling parameter, cell projected area.…”

A comparison of human mesenchymal stem cell osteogenesis in poly(ethylene glycol) hydrogels as a function of MMP‐sensitive crosslinker and crosslink density in chemically defined medium

“…For example, Wang et al () reported that controlling cell shape on micropatterned substrates led to an increase in cytoskeletal tension and augmented BMP‐2‐induced osteogenesis. Other studies, however, have indicated that it is adhesion strength and not cell shape that drives osteogenesis (Khetan et al, ; Wang et al, ). Furthermore, cytoskeleton tension has been shown to be higher when the cells are encapsulated in degradable hydrogels compared with non‐degrading hydrogels, despite having the same amount of adhesion peptides (Khetan et al, ).…”

“…For example, Wang et al (2012) reported that controlling cell shape on micropatterned substrates led to an increase in cytoskeletal tension and augmented BMP-2-induced osteogenesis. Other studies, however, have indicated that it is adhesion strength and not cell shape that drives osteogenesis (Khetan et al, 2013;Wang et al, 2016).…”

Introduction of anti-fouling coatings at the surface of supramolecular elastomeric materials via post-modification of reactive supramolecular additives

“…43 The cells bind to ECM components adsorbed at the material surface through integrin receptors, which upon clustering form focal adhesions that represent a structural link between the cytoskeleton and the biomaterial surface. 44 The cell adhesion and spreading of human kidney (HK-2) cells were studied on the different supramolecular surfaces prior to and after modification with the PEG-BCN hydrophilic ) on the modified surfaces. All the data represented in the graph results from visco-elastic modeling using a Voigt-Voinova model.…”