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

Sep 30, 2026

Uploaded by Jasmine

Immune activity operates within mechanically and geometrically constrained tissue microenvironments, requiring rapid migration and precise effector responses to coordinate innate and adaptive immunity. This review examines how nuclear mechanobiology shapes immune cell functionality, explaining how non-genetic nuclear physical properties—shape, stiffness, and deformability—are controlled and influence trafficking routes and pathogen-killing outcomes. It also summarizes how the nucleus senses spatial constraints, regulates migration, supports extracellular trap formation, and highlights open questions involving chromatin, condensates, and nuclear membrane components.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages36

Reading Time1 h 31 min

AccessFree to download

Introduction

Nuclear mechanobiology and immune cell mechanics

Immune response goals and tissue navigation

NUCLEUS 2026, VOL. 17, NO. 1, 2590843 [https://doi.org/10.1080/19491034.2025.2590843](https://doi.org/10.1080/19491034.2025.2590843) Nuclear mechanobiology rules immune cells’ functions: from differentiation to cell trafficking and pathogen killing Jörg Renkawitz a, Allen Yesin b, Janina Kroll a, Aidan T. Cabral b, Sarah D’Annunzio a, and Hawa Racine Thiam b,c,d,e aBiomedical Center, Walter Brendel Center of Experimental Medicine, Institute of Cardiovascular Physiology and Pathophysiology, Klinikum der Universität, Ludwig Maximilians Universität München, Munich, Germany; bDepartment of Bioengineering, Stanford University, Stanford, CA, USA; cDepartment of Microbiology and Immunology; dSarafan ChEM-H Institute, Stanford University, Stanford, CA, USA; e Biohub, San Francisco, CA, USA 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. ARTICLE HISTORY Received 6 June 2025 Revised 26 October 2025 Accepted 3 November 2025 KEYWORDS Cell migration; chromatin; cytoskeleton-to-nucleus coupling; immune cells; lamins; NETosis; nuclear condensates; nuclear deformation and shape CONTACT Jörg Renkawitz [joerg.renkawitz@med.uni-muenchen.de](joerg.renkawitz@med.uni-muenchen.de) Ludwig Maximilians Universität München, Grosshaderner Str. 9, Planegg/ Martinsried, 82152, Germany; Hawa Racine Thiam [hrthiam@stanford.edu](hrthiam@stanford.edu) Stanford University, 290 Jane Stanford Way, ChEM-H/Neuro Building, Stanford, CA 94305, USA © 2026 The Author(s) . Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. 2 J. RENKAWITZ ET AL. Introduction The nucleus is a defining feature of eukaryotes, where it stores the genome and regulates gene expression. However, the nucleus is also a large and physically complex organelle. In mammalian somatic cells, nuclear diameter ranges between 5 and 20 µm [ 1] and the nucleus can occupy up to 80% of the cell volume [2] . Furthermore, distinct nuclear structures such as chromatin, nuclear lamina, and the nuclear membrane [3] provide the nucleus with physical and mechanical properties, such as shape, size, stiffness, viscoelasticity, deformability, and integrity [4] . These physical properties define the nucleus’s ability to sense, withstand and respond to mechanical forces [5] . Moreover, cells can actively alter nuclear composition, thereby changing the mechanical properties of the nucleus, making it an active material that can adapt over time to the physicochemical properties of the intra- and extracellular sp

FAQs

What does nuclear mechanobiology focus on in immune cells?

It focuses on how non-genetic physical properties of the nucleus, such as shape, stiffness, and deformability, are regulated and how they influence immune functions including migration, trafficking, and pathogen killing.

How can the nucleus act during immune cell migration?

The review describes the nucleus as a deformation sensor and as a regulator that can either enable or break migration depending on mechanical constraints encountered in tissues.

Which nuclear components and molecular features are discussed as open questions?

The review highlights unknowns involving chromatin, nuclear condensates, and components of the nuclear membrane, and how these may impact nuclear mechanics and immune-cell behavior.

Sep 30, 2026

Uploaded by Jasmine