Abstract 5112: To be or not to be a protrusion: Unraveling the determinants of protrusion formation

Abstract

Cellular edge features have been widely studied in recent years due to the interest in cell motility in normal and cancerous cells. Cues from cell interactions with the extracellular environment lead to overall cytoskeletal remodeling and consequently shape changes. The factors that determine the shape of a cell include actin polymerization, myosin II contraction and focal contacts (FCs). Actin based structures like lamellipodia (broad protrusions), ruffles (vertical protrusions) and filopodia (elongated, tapering protrusions) are the major protrusion types described in the scientific literature. However, their subjective classification is a problem when trying to understand mechanisms of protrusion formation in different cell types. The present study makes use of a previously determined computerized morphometric classification technique to distinguish features other than lamellipodia in 1000W rat tracheal epithelial cells. Some of the features identified through previous studies were factor 4, factor 5, factor 7 and factor 16. The aim of the present study was to explore the role of some of the structural components leading to the formation of a protrusion, particularly to a feature defined as factor 7. Integrated morphometry analysis with MetaMorph software was used to study the FC characteristics, while a geographical information system (GIS) software was used to study the FC orientation with respect to a protrusive feature. Small FCs favored factor 7 feature formation. High factor 7 values were observed when the class of FCs without actin became narrower. Paradoxically, where anchored actin cables on FCs showed a positive correlation with factor 7, the inner radius and width of the FC were the only elevated variables. The results suggested that certain populations of FCs with actin, which were narrow but varied in orientation, are important vii ACKNOWLEDGEMENTS As I stand on the verge of fulfilling one of my long cherished goals, I cannot help but take a look back and cherish all the abundant blessings and grace showered upon me by the Almighty. Without the support, guidance and friendship of many a people, this journey would have been incomplete. I would like to express my heartfelt gratitude and sincere appreciation to my research advisor, Dr Carol Heckman for providing the opportunity to work with her and for being a supportive yet daunting mentor all through the years of my study. Her guidance, perseverance and above all her kindness has touched me in many ways. She has not only guided my way to becoming a researcher but also encouraged me to tread paths less taken and be an independent thinker. My special acquaintance with her will always be cherished in the years to come. I would like to thank my committee members: Dr. Peter Gorsevski, Dr. Michael Geusz and Dr. Roudabeh Jamasbi for their positivity, encouragement and invaluable inputs during the course of the study. I would specially like to thank Dr Peter Gorsevski for agreeing to serve as a committee member and for introducing me to biospatial statisti...