Cellular responses to beating hydrogels to investigate mechanotransduction

Yashoda Chandorkar,Reinhard Windoffer,Laura De Laporte,Sjören Schweizerhof,Arturo Castro Nava,Marcel Van Dongen,Ahmed Mourran,Tamás Haraszti,Hang Zhang,Martin Möller,Jens Köhler

doi:10.1038/s41467-019-11475-4

Abstract

Cells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them. While many cell fate processes are dictated by these forces, which are highly synchronized in space and time, abnormal force transduction is implicated in the progression of many diseases (muscular dystrophy, cancer). However, material platforms that enable transient, cyclic forces in vitro to recreate an in vivo-like scenario remain a challenge. Here, we report a hydrogel system that rapidly beats (actuates) with spatio-temporal control using a near infra-red light trigger. Small, user-defined mechanical forces (~nN) are exerted on cells growing on the hydrogel surface at frequencies up to 10 Hz, revealing insights into the effect of actuation on cell migration and the kinetics of reversible nuclear translocation of the mechanosensor protein myocardin related transcription factor A, depending on the actuation amplitude, duration and frequency.

Highlights

Cells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them
To manipulate cells with precisely controlled mechanical forces in space and time, one other approach grows cells on celladhesive stiff elastomeric micropillars (Norland Optical Adhesive (NOA), E ~1 GPa) that are embedded in a thermoresponsive, non-cell-adhesive poly N-isopropyl acrylamide (PNIPAM) hydrogel containing gold nanorods (AuNRs) as photothermal transducers
We demonstrate a light-responsive hydrogel platform, which supports unrestricted cell growth and reversibly applies precise and user-defined mechanical forces on selected cells under physiological conditions. This approach comprises a soft and patterned thin-film ECM-mimetic hydrogel prepared with a ratio of 60/40 mole % N-isopropyl acrylamide (NIPAM) and N-ethyl acrylamide (NEAM) to achieve a volume phase transition temperature (VPTT) around 37 °C, AuNRs for photothermal heating, and a fibronectin/collagen I surface coating for cell attachment (Fig. 1a)

Summary

Introduction

Cells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them. User-defined mechanical forces (~nN) are exerted on cells growing on the hydrogel surface at frequencies up to 10 Hz, revealing insights into the effect of actuation on cell migration and the kinetics of reversible nuclear translocation of the mechanosensor protein myocardin related transcription factor A, depending on the actuation amplitude, duration and frequency. We demonstrate a light-responsive hydrogel platform, which supports unrestricted cell growth and reversibly applies precise and user-defined mechanical forces on selected cells under physiological conditions. This approach comprises a soft and patterned thin-film ECM-mimetic hydrogel prepared with a ratio of 60/40 mole % N-isopropyl acrylamide (NIPAM) and N-ethyl acrylamide (NEAM) to achieve a volume phase transition temperature (VPTT) around 37 °C, AuNRs for photothermal heating, and a fibronectin/collagen I surface coating for cell attachment (Fig. 1a). The Yes-associated protein (YAP) remains in the nucleus before, during and after actuation

Methods

Results

Conclusion