Understanding Cytokinesis and Cell Shape Control
Multicellular living organisms grow from single cells into multicellular, complex systems composed of highly diverse cell-types organized into tissues, which in turn form organs and organ systems. To organize and maintain this complex architecture, the organism must undergo constant renewal through cell proliferation and elimination of unwanted cells. This process of tissue development and homeostasis requires chemical and mechanical information to be sensed by the cells within the tissues, and in turn, interpreted to guide their decision making: to divide, migrate, constrict, or die. Failure in these processes lead to diverse diseases, such as hypertension, degeneration, and cancer.
We have been studying cytokinesis (cell division) as a model cell behavior that incorporates internally generated signals with external mechanical cues to drive healthy cell shape change. We have discerned the mechanics that drive this process, and identified how the cell senses external forces (mechanosensing) and transmits them to changes in the chemical signaling pathways that guide cytokinesis. While we continue to study how these processes direct cytokinesis, we are also learning how these same principles apply to diseases such as cancer. For example, we have identified how mechanical cues guide aberrant behaviors of breast cancer cells. In this case, we found that cancer and non-cancer cells can compete with each other, and due to their unique mechanical properties, the cancer cell (winner cell) can often engulf and kill the non-cancer cell (loser cell).
In another project, we are exploring how cellular growth control pathways lead to defects in cell mechanics. In particular, a key regulatory pathway that guides liver formation and leads to liver cancer if the pathway becomes uncontrolled, also controls the hepatocyte mechanical properties.
Finally, we have found that many of these same principles apply to the development of a mammalian egg where disruption of the cell mechanics machinery causes defects in the formation of a healthy egg. Such mechanics defects could contribute to some types of human infertility and/or birth defects.
You can see information about Dr. Robinson's lab here
Lab Website: Molecular Mechanisms of Cellular Mechanosensing (Robinson Lab)
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Luo T, Srivastava V, Ren Y, Robinson DN. "Mimicking the mechanical properties of the cell cortex by the self-assembly of an actin cortex in vesicles." Appl Phys Lett. 2014 Apr 14;104(15):153701. Epub 2014 Apr 17.
Luo T, Mohan K, Iglesias PA, Robinson DN. "Molecular mechanisms of cellular mechanosensing." Nat Mater. 2013 Nov;12(11):1064-71. doi: 10.1038/nmat3772. Epub 2013 Oct 20.
Kabacoff C, Srivastava V, Robinson DN. "A summer academic research experience for disadvantaged youth." CBE Life Sci Educ. 2013 Fall;12(3):410-8. doi: 10.1187/cbe.12-12-0206.
Kryzak CA, Moraine MM, Kyle DD, Lee HJ, Cubeñas-Potts C, Robinson DN, Evans JP. "Prophase I mouse oocytes are deficient in the ability to respond to fertilization by decreasing membrane receptivity to sperm and establishing a membrane block to polyspermy." Biol Reprod. 2013 Aug 29;89(2):44. doi: 10.1095/biolreprod.113.110221. Print 2013 Aug.
Kee YS, Robinson DN. "Micropipette aspiration for studying cellular mechanosensory responses and mechanics." Methods Mol Biol. 2013;983:367-82. doi: 10.1007/978-1-62703-302-2_20.