Geometric and Bioelectric Cues to Cell Mechanics

As our understanding of multi-scale biological phenomena has improved, it has become increasingly evident that much remains to be learned by examining the mechanical and electrical characteristics of cells. This realization has occurred alongside technological developments enabling us to map out cell-level biological processes with unprecedented spatial and temporal resolution, both in terms of our ability to detect such processes, and increasing specificity of targeted perturbations. In this dissertation, I present the results of research I have conducted to gain further insights into these areas. This research has been decisively multidisciplinary, with inspiration coming from across the natural sciences. It is divided into two broad categories based on the physical phenomena examined in relationship to cellular behavior. One segment is devoted to how colonies of epithelial cells distribute mechanical forces to their environments. In the other segment, I examine the impacts of highly localized electrical stimulation on calcium signaling within colonies of airway smooth muscle cells. The importance of mechanical considerations to cell biology, arising from both the cells themselves as well as their environment, has long been recognized. In the last few decades, however, mechanobiology has seen a resurgence in interest, owing to increased recognition of the physiological impacts mechanical forces and material properties can induce, and the introduction of new techniques to quantify these effects. Traction force microscopy serves as an example of the latter, as it enables us to measure the location, magnitude, and direction of stresses that cells exert on their environments, and it can do so with subcellular spatial resolution and with good temporal resolution. I have employed traction force microscopy in order to better understand how colonies of epithelial cells organize their traction stresses. In the process of doing so, a previously unreported pattern of stress distribution emerged. In collaboration with theorists who developed a new model of how cell shape emerges and is connected with traction stress exertion, we clarified the origins of the new pattern as being a consequence of fluidity within colonies. We further validated this model with a variety of experimental scenarios. Electric fields have also been recognized as important aspects of cell physiology since the 1950s, yet the pace of research in bioelectronics is rapidly increasing. One contributor to this rise in interest is the development of new, nanoscale devices that can interface with cells and subcellular components. This has allowed us to rethink the fundamental science of electric fields interacting with cells, as well as engineer new applications with therapeutic potential. Silicon nanowires are one such type of device, which display many desirable properties such as good biocompatibility, and a wide array of functionalities that can be encoded into their structure during synthesis. I have employed doped silicon nanowires with a p-i-n core-shell dopant profile, which have previously been demonstrated to produce electric currents in response to light stimulation, in conjunction with human airway smooth muscle tissues. I found that nanowire stimulation induced changes in calcium signaling for associated cells, including directly stimulated cells and their neighbors