# Engineering a Quantitative Organ-on-a-Chip Platform for Myogenic Mechanobiology

## TL;DR

A new organ-on-a-chip device was developed to study how mechanical forces influence muscle cell organization and maturation in real time.

## Contribution

A programmable organ-on-a-chip platform with quantitative mechanical control and real-time stress-strain mapping for myogenic cells.

## Key findings

- The platform achieved stable cyclic strain with a linear relationship between applied pressure and membrane deformation.
- Cyclic strain induced uniform cell alignment and increased contractile maturation markers in both cardiomyocytes and skeletal muscle cells.
- Mechanical stimulation promoted structural organization and maturation without altering lineage commitment markers.

## Abstract

Myogenic mechanobiology governs how mechanical cues regulate myocyte organization, alignment, and functional maturation; however, in vitro platforms that enable quantitative control and real-time readout of myogenic mechanical microenvironments remain limited. Here, we engineered a pneumatic-driven organ-on-a-chip platform integrating six parallel culture units and a bead-embedded flexible PDMS membrane to deliver cyclic mechanical strain and enable quantitative stress–strain mapping in cardiomyocytes and skeletal muscle cells. Finite element-guided optimization ensured effective membrane deformation, and the platform generated stable and tunable cyclic strain with a strong linear relationship between applied negative pressure (50–700 mbar) and membrane stress and strain. Plasma treatment combined with type I collagen coating restored myogenic cell adhesion and growth on PDMS to levels comparable to standard culture conditions. Under 13% cyclic strain, both cardiomyocytes and skeletal muscle cells exhibited pronounced and highly uniform alignment, with cellular polarity oriented perpendicular to the stretch axis. Moreover, cyclic loading significantly enhanced the expression of contractile maturation markers, including MYH7 in cardiomyocytes and MYH6 in skeletal muscle cells (all p < 0.05), whereas expression of the differentiation regulator MyoG remained unchanged, indicating that mechanical stimulation preferentially promotes structural organization and contractile maturation rather than lineage commitment. Collectively, this quantitatively programmable organ-on-a-chip represents a bioengineered microdevice for studying myogenic mechanobiology, revealing conserved mechanosensitive alignment and maturation responses across myogenic lineages and providing a versatile framework for biomedical engineering research, disease modeling, and mechanotherapeutic screening.