Physical forces play a crucial role in the development and growth of organisms, influencing their geometrical form, replication, and overgrowth. While extensive research has focused on the effects of these forces on animals, bacteria, which constitute a significant portion of Earth's biomass are not well studied. Bacteria are vital in medicine, biotechnology, and agriculture, forming complex microbiome communities, producing antibiotics, and enhancing soil health. Understanding bacterial mechanics and their responses to physical forces is crucial to understanding their survival, adaptability, and roles in various ecosystems.

This dissertation aims to advance our understanding of bacterial biomechanics and mechanobiology by developing innovative tools and methodologies. The first chapter presents a novel method for determining the Young's modulus of bacterial cell envelope, a physical barrier protecting the content of bacteria. Combining a microfluidic approach for applying pressure to individual bacteria with optimization-based inverse finite element analysis (FEA) quantifies Young's modulus for three bacterial species, providing a robust framework for analyzing bacterial mechanical properties.

The second chapter investigates the role of the VxrAB two-component system (TCS) within the cell envelope of Vibrio cholerae, the bacterium responsible for cholera. Our research examines the sensitivity and responsiveness of VxrAB to mechanical stress, revealing that bacteria can sense and respond to mechanical stimuli through this regulatory system, underscoring the importance of mechanical cues in bacterial physiology.

The third chapter addresses the technical challenges in fabricating microfluidic devices, which are essential for conducting controlled experiments on bacterial biomechanics and mechanobiology. We established a method to produce precise and reliable microfluidic systems for studying bacterial mechanics by optimizing nanofabrication procedures.

This dissertation's uniqueness lies in its interdisciplinary approach, combining mechanical engineering, microbiology, and advanced fabrication techniques. The methodologies developed here enable a deeper understanding of bacterial physiology and mechanics, facilitating detailed observations and analyses of bacterial responses to physical forces. Future research can build on this dissertation's foundation to further elucidate the complex relationships between mechanical properties, bacterial physiology, and pathogenicity, ultimately contributing to advances in microbiology, medicine, and biotechnology.