Quantitative Estimation of Cell Mechanical Cues using Elastic Micropillars
by Tanmaya Sethi
Date of Examination:2024-02-06
Date of issue:2025-01-24
Advisor:Prof. Dr. Andreas Janshoff
Referee:Prof. Dr. Sarah Köster
Referee:Prof. Dr. Michael Meinecke
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Abstract
English
Within the intricate landscape of the cellular microenvironment, the inter- play between biochemical and physical signaling emerges as a decisive force shaping the physiology and functions of living cells. Recent insights underscore the pivotal role of cells in responding to the multifaceted dynamics of their surroundings, establishing a critical foundation for unraveling the complexities inherent in normal and diseased processes. A contemporary understanding positions cells as dynamic entities actively navigating their microenvironment through intricate physical forces. The concept of mechanotransduction emphasizes the continuous interplay between biochemical and mechanical signaling, necessitating the development of sophisticated tools for the precise quantification of cellular forces across diverse time and length scales. However, quantifying force in cell biology presents a unique challenge, prompting the conceptualization of force measurement systems comprising a force sensor and an associated measuring instrument. Early techniques, exemplified by traction microscopy, faced computational challenges, paving the way for PDMS micropillars to emerge as pivotal tools for measuring contractile forces. Beyond their utility in cardiomyocytes, micropillars find applications in neuronal and cancer studies, unraveling the intricate mechanical aspects of cellular responses. Their microscale precision and adaptability for high-throughput studies underscore their efficiency in advancing cellular force quantification methodologies. This thesis is structured around two substantive chapters, each delving into distinct aspects of cellular mechanics using elastic micropillars. Chapter 2 intricately examines the application of elastic micropillars as localized force sensors, with a specific focus on probing the contraction and relaxation processes of hiPSC-CMs. This chapter aims to unravel the dynamics of force generation within cardiomyocytes, exploring varied spatial arrangements of micropillars and cells, along with investigating the effects of cardiovascular drugs on cardiomyocyte contractility. In Chapter 3, the narrative shifts as micropillars take on a new role as agents of lateral confinement for epithelial cell sheets. This transition transforms into a detailed quantitative analysis, centering on modulating cell sheet behavior through lateral constraint. The chapter provides nuanced insights into the mechanical responses of epithelial cell sheets under controlled spatial conditions, shedding light on the behavior of cells with impaired tight junctions in the context of micropillars. Overall this work shows the versatile use of micropillars concerning quantification of different cellular mechanical cues.
Keywords: Micropillar, Cell mechanics