Bioengineering Lecture

A fundamental issue in cell biology and tissue engineering is how to control the sizes and shapes of cells and tissues. The current engineering relies on the theory that cells use intracellular molecular feedback circuits in response to extracellular morphogen gradients and positional cues of premade scaffolds to direct cytoskeleton mechanics, thereby controlling cell and tissue morphologies. Here, we show two studies of mechanics-based self-organizations of cell shapes and tissue morphologies. First, we demonstrate the conditions under which adult epithelial cells and type I collagen molecules can self-organize into unbranched tubules that are around one centimeter long and hundreds of micrometer wide without preexisting positional cues from scaffolds or templates. These tubules develop apicobasal polarity and lumens as those found in situ. In particular, tubule formation involves correlated and persistent cell motions, and long-range (~ 600 micrometers) mechanical interactions but not gradients of soluble factors. Our findings illustrate the feasibility of building long tubules under scaffold-free conditions that can be extended to the engineering of other organs. Second, we show that cells could pattern their shape without the involvement of molecular feedback circuits, but instead through a geometry-dependent positive feedback loop. Such a feedback loop arises from the boundary effect of cell shape and can in turn guide the spatial patterning of signaling molecules, highlighting a novel connection between downstream mechanical output and upstream signaling dynamics.