Dynamically Modulated Core-Shell Microfibers to Study the Effect of Depth Sensing of Matrix Stiffness on Stem Cell Fate

It is well known that extracellular matrix stiffness can affect cell fate and change dynamically during many biological processes. Existing experimental means for in situ matrix stiffness modulation often alters its structure, which could induce additional undesirable effects on cells. Inspired by the phenomenon of depth sensing by cells, we introduce here core-shell microfibers with a thin collagen core for cell growth and an alginate shell that can be dynamically stiffened to deliver mechanical stimuli. This allows for the maintenance of biochemical properties and structure of the surrounding microenvironment, while dynamically modulating the effective modulus felt by cells. We show that simple addition of Sr2+ in media can easily increase the stiffness of initially Ca2+ cross-linked alginate shells. Thus, despite the low stiffness of collagen cores (<5 kPa), the effective modulus of the matrix felt by cells are substantially higher, which promotes osteogenesis differentiation of human mesenchymal stem cells. We show this effect is more prominent in the stiffening microfiber compared to a static microfiber control. This approach provides a versatile platform to independently and dynamically modulate cellular microenvironments with desirable biochemical, physical, and mechanical stimuli without an unintended interplay of effects, facilitating investigations of a wide range of dynamic cellular processes.

Automated summary

It has been shown that dynamically modulating the effective modulus felt by cells in their microenvironment by increasing stiffness can promote osteogenesis differentiation of human mesenchymal stem cells. Introducing core-shell microfibers with a thin collagen core and a dynamically stiffened alginate shell allows for this without altering the surrounding microenvironment's structure. This approach offers a versatile platform for investigating a wide range of dynamic cellular processes by independently and dynamically modulating cellular microenvironments with desirable biochemical, physical, and mechanical stimuli.