Engineering soft microdevices for the mechanical characterization and stimulation of microtissues

Introduction

As living beings move, touch, or grow, the tissues within them are subject to mechanical stresses that act over minutes, hours, or days. These efforts play a critical role at all stages of life, from early embryonic development to homeostasis in adult tissues or disease progression.

Mechanobiology Overview

Mechanobiology has emerged in response to this realization and has led to many discoveries on mechanosensitive pathways in individual cells. However, we are still very far from relating the single-cell behavior to the response within a real tissue that contains mixtures of cell types organized in complex 3D structures.

Project Goals

In this project, we will expand mechanobiology to 3D tissues by developing a new class of micro-devices, based on soft robotics and metamaterials, for active mechanical forcing of spheroids and organoids. We will couple this active forcing with multiscale cytometry methods that we have pioneered, in addition to concepts from many-body soft matter physics.

Research Objectives

This will allow us to understand how the rheological responses of individual cells add up to result in the global tissue rheology. The outcome is a new paradigm to probe phenotypic changes, such as:

1. The epithelial-mesenchymal transition in a cancer model
2. Cellular differentiation and 3D organization in a maturing organoid

Conversely, we will map how global mechanical stresses are transferred to individual cells that in turn respond to the forces locally.

Engineering Strategies

This will allow us to engineer dynamical forcing strategies to guide the biological response of specific populations within a complex co-culture. When applied to developing organoids, this will lead to strategies to mature individual cell types, with a view to using them for cell therapy.

Cancer Model Applications

In the case of cancer models, we will identify mechanosensitive pathways that can be targeted by drugs to treat real tumors.

Conclusion

By working on the joint cutting edge of technology, physics, and biology, we will manipulate in vitro models with real impact on human health.