Biophysical Regulation of Cell Behavior-Cross Talk between Substrate Stiffness and Nanotopography.

Xiaosong Gu,Kai Wang,Kam W. Leong,Yong Yang

doi:10.1016/j.eng.2017.01.014

Xiaosong Gu, Kai Wang + Show 2 more

Open Access

https://doi.org/10.1016/j.eng.2017.01.014

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Abstract

The stiffness and nanotopographical characteristics of the extracellular matrix (ECM) influence numerous developmental, physiological, and pathological processes in vivo. These biophysical cues have therefore been applied to modulate almost all aspects of cell behavior, from cell adhesion and spreading to proliferation and differentiation. Delineation of the biophysical modulation of cell behavior is critical to the rational design of new biomaterials, implants, and medical devices. The effects of stiffness and topographical cues on cell behavior have previously been reviewed, respectively; however, the interwoven effects of stiffness and nanotopographical cues on cell behavior have not been well described, despite similarities in phenotypic manifestations. Herein, we first review the effects of substrate stiffness and nanotopography on cell behavior, and then focus on intracellular transmission of the biophysical signals from integrins to nucleus. Attempts are made to connect extracellular regulation of cell behavior with the biophysical cues. We then discuss the challenges in dissecting the biophysical regulation of cell behavior and in translating the mechanistic understanding of these cues to tissue engineering and regenerative medicine.

Highlights

A growing body of literature shows that cell fate can be dictated by the stiffness and topographical characteristics of the extracellular matrix (ECM)
We first review the effects of substrate stiffness and nanotopography on cell behavior, and focus on intracellular transmission of the biophysical signals from integrins to nucleus
On a PAAm substrate with a gradient of stiffness that is linearly varied from ~1 kPa to 240 kPa across 2 mm, National Institute of Health (NIH) 3T3 fibroblastic and neuroblastoma cells display a rounded morphology with diffuse focal adhesions on the softer region, but are well spread with defined focal adhesions on the stiffer region, as shown in Fig. 7(a) [239]

Summary

Introduction

A growing body of literature shows that cell fate can be dictated by the stiffness and topographical characteristics of the extracellular matrix (ECM). C2C12 mouse myoblasts exhibit definitive actomyosin striations only on polyacrylamide (PAAm) gels with a stiffness that is typical of normal muscle, but not on softer gel or stiffer glass substrate [33]. Despite similarities in phenotypic manifestations, the interwoven effects of stiffness and nanotopographical cues on cell behavior have not been well described [51]. We first review the effects of substrate stiffness and nanotopography on cell behavior, and focus on intracellular transmission of the biophysical signals from integrins to nucleus. We discuss the challenges in dissecting the biophysical regulation of cell behavior and in translating the mechanistic understanding of these cues to tissue engineering and regenerative medicine

Stiffness cues

Nanotopographical cues

Interwoven substrate nanotopographical and stiffness cues

Intracellular transduction of biophysical signals

Similarity between substrate stiffness and nanotopographical modulation

Theoretical modeling

Perspectives

Mechanistic understanding of biophysical regulation

Translation of biophysical regulation from 2D to 3D

Findings

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