Poster

Mechanical properties of murine microglia in a model of Alzheimer's disease

Justyna Śmiałek-Bartyzel¹, Sara Metwally¹, Jakub Frydrych², Krzysztof Łukowicz², Beata Grygier², Ewa Trojan², Agnieszka Basta-Kaim², Małgorzata Lekka¹

Contact: 

Microglial cells are the resident macrophages in the central nervous system. These cells constitute an important element of the immune response in the brain and the spinal cord. Chronic inflammatory activation of microglial cells is observed in various diseases, including cancer and neurodegenerative diseases.
The presented study aimed to investigate the biomechanical properties of microglia in the context of inflammation, with a specific focus on cellular elasticity. Primary microglial cells were isolated from 1-2 days-old mice, and biomechanical measurements were performed using atomic force microscopy (AFM), which worked in force spectroscopy mode. Data were collected over the cell nucleus, and the Hertz model was used to evaluate the mechanical properties of cells, which were quantified using elastic modulus (E). Biomechanical measurements were conducted on primary microglial cells obtained from the knock-in murine model of late-onset Alzheimer's disease (APP^NLF/NLF) and wild-type mice (WT). Isolated cells were cultured in the presence or absence of bacterial endotoxin (lipopolysaccharide, LPS).
We observed significant changes in the morphology of LPS-treated cells (both for WT microglial cells and APP^NLF/NLF microglial cells) contrary to non-stimulated cells. In basal conditions, no differences in mechanical properties of WT microglia and APP^NLF/NLF microglia were observed. However, treatment of microglia with lipopolysaccharide significantly increased the elastic modulus for APP^NLF/NLF microglial cells (E = 2.37 ± 0.15 kPa vs E = 3.44 ± 0.26 kPa for non-treated APP^NLF/NLF and LPS-treated APP^NLF/NLF, respectively, p = 0.05, One-way ANOVA with post-hoc Tukey's multiple comparisons test). Altogether, these results indicate that inflammation, as mimicked by LPS treatment, can alter the biomechanical characteristics of microglial cells, emphasizing the impact of inflammatory stimuli on cellular biomechanics in disease conditions.

Acknowledgments
This study was financed by the National Science Centre (Poland), project no. UMO-2021/43/B/NZ4/01133 (NCN, OPUS).