- Titel
- EXPLORING NON-LINEAR STRAIN STIFFENING IN CELLULAR AGGREGATES
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-968936
- Datum der Einreichung
- 25.10.2024
- Datum der Verteidigung
- 14.03.2025
- Abstract (EN)
- In cell clusters, the prominent factors at play encompass contractility-based enhanced tissue surface tension, and cell unjamming transition. Both effects share outcomes of inducing significant elongation in cells. This elongation is so substantial that it surpasses the limits of linear elasticity, thereby giving rise to additional effects. To investigate these effects, I employ Atomic Force Microscopy (AFM) to analyze how the mechanical properties of individual cells change under such considerable elongation. My selection of cell lines includes MCF-10A, chosen for its pronounced demonstration of the extended differential adhesion hypothesis (eDAH), and MDA-MB-436, selected due to its manifestation of cell unjamming behavior. In the AFM analysis, I observe a common trend in both cases: as elongation increases, both cell lines exhibit strain stiffening. Notably, this effect is more prominent in MCF-10A compared to MDA-MB-436. Subsequently, I employ AFM on a dynamic range of 1-200Hz to probe the mechanical characteristics of cell spheroids, focusing on both surface and bulk mechanics. My findings align with the results from single cell investigations. Specifically, MCF-10A cells, characterized by strong contractile tissue tension, exhibit the greatest stiffness on their surface. Conversely, MDA-MB-436 cells, which experience significant elongation, showcase their highest stiffness within the bulk region. As cancerous spheroids are stiffer and nuclei-dominated in the bulk, the stiffening effect is particularly pronounced in such area where nuclei are densely packed. The squeezing cell needs shape-induced strain stiffening to achieve a successful squeeze-through. This stiffening, which can be valued as yield stress (YS), provides the rigidity required to push through their environment. By modeling the Young's modulus equation, I quantified the YS for MDA-MB-436 squeezing cells. I discovered an adaptive mechanism where cells stiffen during the squeeze-through event and then soften after repositioning. I conclude the strain stiffening is favoring the cancerous cells' movement, both mechanically and biologically. Thus, the concept of single cell strain stiffening emerges as a crucial element in understanding the mechanics of cellular aggregates. The YS, derived from strain stiffening, effectively captures the mechanical resistance cells face during movement, making it a promising parameter to include in the current state diagram.
- Freie Schlagwörter (EN)
- Cancer, Jamming, Strain Stiffening, Viscoelasticity, Cell Tracking
- Klassifikation (DDC)
- 530
- Den akademischen Grad verleihende / prüfende Institution
- Universität Leipzig, Leipzig
- Version / Begutachtungsstatus
- angenommene Version / Postprint / Autorenversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-968936
- Veröffentlichungsdatum Qucosa
- 29.04.2025
- Dokumenttyp
- Dissertation
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY-NC-ND 4.0