The motility of normal and cancer cells in response to the combined influence of substrate rigidity and anisotropic microstructure

TL;DR

This study investigates how normal and cancerous fibroblastic cells respond differently to substrate stiffness and microstructure, revealing distinct migration and morphology behaviors influenced by environmental cues.

Contribution

It provides a systematic analysis of how substrate rigidity and microtopography differentially affect normal and cancer cell motility and morphology.

Findings

Normal cells' polarization depends on substrate microtopography and rigidity.

Cancer cells' migration is uncorrelated and disperses more with increased rigidity.

Distinct responses highlight differences in environmental cue processing between cell types.

Abstract

Cell adhesion and migration are strongly influenced by extracellular matrix (ECM) architecture and rigidity, but little is known about the concomitant influence of such environmental signals to cell responses, especially when considering cells of similar origin and morphology, but exhibiting a normal or cancerous phenotype. Using micropatterned polydimethylsiloxane substrates (PDMS) with tuneable stiffness (500kPa, 750kPa, 2000kPa) and topography (lines, pillars or unpatterned), we systematically analyse the differential response of normal (3T3) and cancer (SaI/N) fibroblastic cells. Our results demonstrate that both cells exhibit differential morphology and motility responses to changes in substrate rigidiy and microtopography. 3T3 polarization and spreading are influenced by substrate microtopography and rigidity. The cells exhibit a persistent type of migration, which depends on the substrate anisotropy. In contrast, the dynamic of SaI/N spreading is strongly modified by the substrate topography but not by substrate rigidity. SaI/N morphology and migration seem to escape from extracellular cues: the cells exhibit uncorrelated migration trajectories and a large dispersion of their migration speed, which increases with substrate rigidity.