Max Perutz Labs - Diz-Munoz

The Question

We study the remarkable biophysics that arises from living composite interfaces. These are ubiquitous in biology: from the cell surface to cell-extracellular matrix interfaces in tissues. In such systems, the synergy of the distinct biophysical characteristics of the components leads to emergent properties which we believe underlie the extraordinary morphological adaptability of living matter. Immune cells, which constantly change shape as they patrol, squeeze through and remodel tissues, are a particular focus of our work. Working across cell and tissue types, including patient samples, we reveal novel mechanisms of encoding biological information that reside in the coupling of time and spatial scales, showing how active materials give rise to complexity at the meso- and cellular scales.

The Approach

The Diz-Muñoz lab applies a collaborative, interdisciplinary, and engineering-inspired approach to elucidate mechanical control mechanisms within biological composites. In all aspects of our work, the development of novel tools and approaches that enable us to apply our soft matter perspective to living systems has been critical. These tools range from synthetic biology to cellular bioengineering, advanced microscopy and modelling. Atomic force microscopy is central to our work, and we have pioneered its use to measure cell and tissue mechanics. This wide range of tools and approaches allows us to identify unifying biomechanical principles and unlock the potential of composite materials for both fundamental biology and applied biomedical science.

Spotlights

Caging of membrane-to-cortex attachment proteins can trigger cellular symmetry breaking

Cells must break shape symmetry as they move, differentiate, and divide. Here, we identified a mechanism for the control of this critical process. Combining in silico, in vitro, and in cellula work, we showed that membrane fluidity and the length of the specialized proteins that link the membrane to the actin cortex work synergistically to control cell surface mechanics.
https://www.biorxiv.org/content/10.1101/2024.10.14.618153v1

The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics

This study combined synthetic biology, advanced biophysical techniques, and cryo-electron tomography visualization to examine the cell surface in unprecedented detail. This allowed us to identify the nanoscale distance between the plasma membrane and the actomyosin cortex as a key geometrical parameter for the control of cell surface mechanics.

www.nature.com/articles/s41467-026-72845-3

MechanoMaST – a multimodal pipeline for spatially registering mechanical and transcriptomic tissue data

Tissue mechanics are critical for development and the normal functioning of tissues, and mechanical disruption is often a hallmark of disease states. Here, we introduced a pipeline that allows for the precise spatial registration of tissue stiffness measurements and gene expression. MechanoMaST will enable researchers to gain a deeper understanding of the molecular origins of tissue stiffness.

www.biorxiv.org/content/10.64898/2026.08.29.747727v1

Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles

We showed how immune-like cells read out their surface topography and utilize actin and plasma membrane biophysics to interpret their surroundings, allowing them to navigate complex environments as they migrate.

https://www.nature.com/articles/s41467-023-41173-1

Cell Surface Mechanics Gate Embryonic Stem Cell Differentiation

We discovered that the mechanics of the plasma membrane acts as a gatekeeper of cell identity. This showed that physical forces, not only chemical signals, help decide what a cell becomes.

https://www.sciencedirect.com/science/article/pii/S1934590920305336?via%3Dihub