Detailed viscoelastic mapping for application to immune cells
(2025) EMBO Workshop Immunobiophysics: From fundamental physics to understanding the immune response — Location: Les Houches, France (27.April.2025)
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- Abstract
- Macrophages are innate immune cells, serving as sentinels of the immune system and keepers of homeostasis [1]. Like other immune cells, macrophages perform inherently mechanical functions, from forming dynamic interfaces with healthy and senescent cells, to reshaping themselves and their surrounding matrix to enable migration through tissue. In addition, macrophages actively sample and clean their environment through processes such as pinocytosis and phagocytosis [2]. In essence, macrophages navigate a life defined by force generation and structural deformability. In fact, macrophages possess a distinct cytoskeleton that is structurally and morphologically organized in a manner unique to immune cells compared to non-immune cells. They generate specialized actin structures, such as podosomes (Fig. 1B) as well as extensive lamellae and lamellipodia, to maintain constant awareness of their mechanical environment. At the same time, macrophages must undergo significant deformations to protect their nucleus during migration through dense and complex extracellular matrices. Using atomic force microscopy (AFM) on human monocyte-derived macrophages, we generate and analyze detailed mechanical maps of differentiated macrophages. Harnessing the potential of state-of-the-art mechanical model that account for the time-dependent, viscous behaviour of biological material, and correct for the bottom effect due to the presence of a glass substrate [3], we developed and scaled up an automated analysis pipeline that allows us to investigate even the thinnest features of the cell (Fig. 1A). When applied to mechanically intricate macrophages, this approach provides valuable insights into the heterogeneity of macrophage mechanics, enabling comparative analysis of the mechanical features across different macrophage subtypes. By exploiting this powerful analysis tool to acquire high-resolution viscoelasticity maps, we explore the heterogeneity of macrophage mechanics. Combining this method with targeted functional assays and confocal microscopy, we aim to understand the capacity of macrophage subtypes to generate forces and migrate, with the goal of extending this approach to investigate diseaserelevant functional states of macrophages.
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Oncina-Gil, P., & et al. (2025). Detailed viscoelastic mapping for application to immune cells. EMBO Workshop Immunobiophysics: From fundamental physics to understanding the immune response, Les Houches, France. https://hdl.handle.net/2078.5/268054