# Nuclear mechanobiology rules immune cells’ functions: from differentiation to cell trafficking and pathogen killing

## TL;DR

This paper reviews how the physical properties of the nucleus influence immune cell behavior, including movement and pathogen killing.

## Contribution

The paper provides a framework for understanding how nuclear mechanobiology regulates immune cell functions through physical properties.

## Key findings

- Nuclear shape, stiffness, and deformability directly impact immune cell trafficking and effector functions.
- The nucleus acts as a sensor for spatial constraints and can enable or hinder cell migration.
- Nuclear extracellular traps are used by immune cells to kill pathogens.

## Abstract

The immune system functions within tissue microenvironments of mechanical and geometrical constraints. Within these constraints, immune cells must rapidly move and execute effector functions to regulate innate and adaptive immunity. Here, we review the impact of nuclear mechanobiology on immune cell functionality. We define how non-genetic physical properties of the nucleus such as shape, stiffness and deformability are regulated and directly impact immune cell functions ranging from trafficking routes to pathogen killing. We highlight that studying immune cells allowed breakthroughs in understanding how the nucleus acts as a sensor for spatial constraints, as a break or enabler for cell migration, and as an extracellular trap to kill pathogens. Further, we discuss the unknowns of nuclear mechanobiology and consider the impact of chromatin, condensates, and nuclear membrane components. Together, this review provides an overarching framework of the cellular, physical, and immunological principles of nuclear mechanobiology in immune cells.