# A biohybrid system to reconstruct epithelial morphomechanics in vitro

## TL;DR

A new biohybrid system called BIOPRECS mimics how epithelial tissues compact in response to muscle contraction, enabling detailed study of tissue mechanics and morphogenesis.

## Contribution

The novel contribution is the development of BIOPRECS, a programmable in vitro system that replicates multi-axial epithelial compaction and organ-specific architectures.

## Key findings

- BIOPRECS enables programmable multi-axial epithelial compaction mirroring in vivo processes.
- The system allows examination of tissue-scale folding and subcellular deformation responses.
- It reproduces organ-specific epithelial architectures similar to those in the lung, intestine, and stomach.

## Abstract

Epithelial tissue compaction driven by smooth muscle contraction is central to epithelial morphogenesis and mechanotransduction. However, in vitro systems that recapitulate this mechanical process – especially those capable of mimicking the anisotropic and multi-axial nature of smooth muscle contraction – remain limited. Here, we present the biohybrid programmable epithelial tissue compaction system (BIOPRECS), consisting of an overlying contraction-responsive epithelial tissue (ET) and underlying thermo-responsive contractile hydrogel (CH). By coupling isotropic hydrogel contraction with defined epithelial geometric anisotropy, BIOPRECS enables programmable multi-axial epithelial compaction that mirrors in vivo processes. Its in situ culture-compatible setup allows straightforward examination of both tissue-scale folding and subcellular deformation, including cytoplasmic and nuclear responses. Furthermore, by modulating tissue geometry and boundary conditions, BIOPRECS reproduces organ-specific epithelial architectures reminiscent of those observed in the lung, intestine, and stomach. This system has a significant potential to become a powerful tool for investigating how mechanical compaction regulates epithelial morphogenesis and mechanotransduction.

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