Uses for Kinetic Mass Balances in Bioengineering
- pdf version of the abstract

Macroscopic mass balances can be used to track many physical substances as long as the reactions that degrade the substance are included in the model. Examples in the literature in which these balances have been used include David Ho and co-workers’ analysis of HIV viral load during the course of drug treatment and Sturis and co-workers’ modeling of glucose and insulin interactions in the body. David Ho et al.’s analysis derived from a desire to answer the question: How does one know if HIV has actually been cured by drug treatment?
As a post-doctoral research associate in Harold Erickson’s lab at Duke University Medical Center, I employed mass balances to better understand the in vitro assembly dynamics of FtsZ, a prokaryotic homolog of tubulin. This molecule, which is essential for bacterial cytokinesis, forms a ring around the inner surface of the cytoplasmic membrane and constricts to cause septation. As part of understanding how FtsZ forms a stable ring structure that can constrict when needed, we attempted to determine whether FtsZ’s assembly was isodesmic (each bond in the protofilament has an identical equilibrium constant) or cooperative (protofilaments only become stable after forming an oligomeric nucleus). Using macroscopic mass balances and assuming the isodesmic assembly model to be correct, we predicted how many FtsZ—FtsZ bonds would be formed or broken upon injection of FtsZ solutions into various buffers, GDP, GTP, and/or FtsZ molecules. We then calculated the heat expected to be released or absorbed if those bonds were formed or broken. Finally we performed isothermal titration calorimetry (ITC) experiments to measure the actual heat given off by the injections for these conditions. Our conclusions were that injections of FtsZ into buffers containing GDP (but no GTP) produced results consistent with the isodesmic assembly model. Injections of FtsZ into buffers containing GTP, on the other hand, produced results that can only be consistent with a cooperative model for assembly. This conclusion has spurred research to find the physical source of such cooperativity as it is counterintuitive that a single-stranded protofilament could exhibit cooperative assembly.

Biographical Note

Michael Caplan was born and raised in New Orleans, Louisiana where he attended Metairie Park Country Day School until 1986 and was graduated from Jesuit High School summa cum laude in 1991. He was then enrolled at The University of Texas at Austin. Summer employment at the Southern Regional Research Center of the United States Department of Agriculture in New Orleans, Louisiana with Dr. Ranjit Kadan, at British Petroleum Exploration Alaska under the guidance of Marty Fossum and Byron Haynes, and at The University of Texas at Austin in the laboratory of Dr. Douglas Lloyd was completed between 1991 and 1996.
Michael was graduated from The University of Texas at Austin in May of 1996 with a B.A. in Plan II (a liberal arts honors program) and a B.S. in Chemical Engineering with honors. He is an active member of Tau Beta Pi and Phi Beta Kappa. He received a Whitaker Foundation Graduate Fellowship and enrolled in the Ph.D. program at MIT in Chemical Engineering in August 1996. Working with co-advisors Dr. Douglas Lauffenburger and Dr. Roger Kamm, he produced a thesis titled “Principles for Rational Design of a Self-assembling, Oligopeptide Biomaterial” and graduated in June 2001. As a post-doctoral research associate in the laboratory of Dr. Harold Erickson in the Department of Cell Biology at the Duke University Medical Center, he performed research on the in vitro assembly dynamics of the bacterial cell division protein, FtsZ. Michael joined the faculty of Arizona State University’s Harrington Department of Bioengineering in January 2003 where he has started research on reverse-engineering the extracellular matrix — in particular studying the mechanisms by which proteins of the basement membrane control cell behavior.