Linda Hansen

Cellular tensegrity: exploring how mechanical changes in the cytoskeleton regulate cell growth, migration, and tissue pattern during morphogenesis.

Publisher Summary This chapter focuses on the role of the intracellular cytoskeleton (CSK) in cell shape determination and tissue morphogenesis. The role of mechanical changes in the CSK during embryological development is reviewed. The chapter focuses on the mechanism by which mechanical forces are transmitted across the cell surface and through the CSK, as well as how they regulate cell shape. An analysis of the biomechanical basis of cell shape control addresses two central questions: (1) how do changes in mechanical forces alter CSK organization, and (2) how do changes in CSK structure regulate cell growth and function. The results from recent studies showing that the CSK can respond directly to mechanical stress are also reviewed. The particular type of mechanical response that living cells exhibit is consistent with a theory of CSK architecture that is based on tensional integrity and is known as “tensegrity”. Inherent to the tensegrity model is an efficient mechanism for integrating changes in structure and function at the tissue, cell, nuclear, and molecular levels. The chapter explores the possibility that CSK tensegrity may also provide a mechanical basis for cell locomotion as well as a structural mechanism for coupling mechanical and chemical signaling pathways inside the cell.

Principles of Tissue Engineering and Reconstruction Using Polymer-Cell Constructs

The fields of materials science, cell and molecular biology, and surgical reconstruction are merging to create new devices for surgical transplantation and reconstructive applications. The field of artificial devices for implantation has matured over the last 40 years. Likewise, the field of transplantation and tissue reconstruction has undergone enormous change and improvements over the last 30 years. It has been proposed that these fields merge to create new tissue substitutes for functional replacement, therapy or reconstructive applications. Over the last five years, our lab has experimented with the concept of using man-made, biodegradable polymer systems as scaffolding for cell implantation devices. They have been designed to maximize diffusion parameters allowing nutrient exchange, gas exchange, and waste exchange. Vascular ingrowth occurs in the implant with subsequent resorption of the original polymer. This leaves a permanently engrafted new tissue which is a chimera of donor cells for functional replacement and recipient mesenchymal elements including blood vessels and supporting tissue. We have experimented in several model systems including hepatocyte implants, chondrocyte implants for cartilage reconstruction, urethelial implants for urinary reconstruction, and more recently small bowel and bone. Across this broad front of tissue types, much new knowledge has been gained and there continues to be hope that this will achieve clinical application.