This dissertation features a compilation of studies concerning the biophysics of multicellular systems. I explore eukaryotic systems across length scales of the cell cytoskeleton to macroscopic scales of tissues. I begin with a general overview of the natural phenomena of life and a philosophy of investigating developmental systems in biology.…
This dissertation features a compilation of studies concerning the biophysics of multicellular systems. I explore eukaryotic systems across length scales of the cell cytoskeleton to macroscopic scales of tissues. I begin with a general overview of the natural phenomena of life and a philosophy of investigating developmental systems in biology. The topics covered throughout this dissertation require a background in eukaryotic cell physiology, viscoelasticity, and processes of embryonic tissue morphogenesis. Following a brief background on these topics, I present an overview of the Subcellular Element Model (ScEM). This is a modeling framework which allows one to compute the dynamics of large numbers of three-dimensional deformable cells in multi-cellular systems. A primary focus of the work presented here is implementing cellular function within the framework of this model to produce biologically meaningful phenotypes. In this way, it is hoped that this modeling may inform biological understanding of the underlying mechanisms which manifest into a given cell or tissue scale phenomenon. Thus, all theoretical investigations presented here are motivated by and compared to experimental observations. With the ScEM modeling framework I first explore the passive properties of viscoelastic networks. Then as a direct extension of this work, I consider the active properties of cells, which result in biological behavior and the emergence of non-trivial biological phenotypes in cells and tissues. I then explore the possible role of chemotaxis as a mechanism of orchestrating large scale tissue morphogenesis in the early embryonic stages of amniotes. Finally I discuss the cross-sectional topology of proliferating epithelial tissues. I show how the Subcellular Element Model (ScEM) is a phenomenological model of finite elements whose interactions can be calibrated to describe the viscoelastic properties of biological materials. I further show that implementing mechanisms of cytoskeletal remodeling yields cellular and tissue phenotypes that are more and more biologically realistic. Particularly I show that structural remodeling of the cell cytoskeleton is crucial for large scale cell deformations. I provide supporting evidence that a chemotactic dipole mechanism is able to orchestrate the type of large scale collective cell movement observed in the chick epiblast during gastrulation and primitive streak formation. Finally, I show that cell neighbor histograms provide a potentially unique signature measurement of tissue topology; such measurements may find use in identifying cellular level phenotypes from a single snapshot micrograph.
Mitochondria are organelles found in the cytoplasm of eukaryotic cells. They are composed of an outer membrane and an inner membrane. The outer membrane faces the cellular cytoplasm, while the inner membrane folds back on itself multiple times, forming inner folds, called cristae. The space between the two membrane layers…
Mitochondria are organelles found in the cytoplasm of eukaryotic cells. They are composed of an outer membrane and an inner membrane. The outer membrane faces the cellular cytoplasm, while the inner membrane folds back on itself multiple times, forming inner folds, called cristae. The space between the two membrane layers is called the intermembrane space, and the space within the inner membrane is called the matrix.
Lynn Petra Alexander Sagan Margulis was an American biologist, whose work in the mid-twentieth century focused on cells living together in a mutually advantageous relationship, studied cells and mitochondria in the US during the second half of the twentieth century. She developed a theory for the origin of eukaryotic cells,…
Lynn Petra Alexander Sagan Margulis was an American biologist, whose work in the mid-twentieth century focused on cells living together in a mutually advantageous relationship, studied cells and mitochondria in the US during the second half of the twentieth century. She developed a theory for the origin of eukaryotic cells, that proposed two kinds of structures found in eukaryotic cells mitochondria in animals, and plastids in plantsÑwere once free-living bacteria that lived harmoniously and in close proximity to larger cells, a scenario called symbiosis. Margulis proposed that the larger cells eventually engulfed the free-living bacteria, resulting in cells living inside other cells, a situation called endosymbiosis. Margulis'theory became called the serial endosymbiosis theory (SET). Her work contributed to explanations of the evolution and development of life, as eukaryotic cells comprise most multicellular organisms, including their embryos.
