Physics Department, PHD Dissertation Defense, James Kingsley - “Modeling of Active and Passive Transport in Biological”

Thursday, June 27, 2019
11:00 am

Location:

Floor/Room #: 
109

Active and passive transport play complementary and critical roles in biological systems.  Passive transport via diffusion enables chemical reactions to proceed, and allows reactants and products to travel around cells.  However, for larger products and longer length scales, passive transport is insufficient, leading to various forms of active processes, which can transport material further and faster than diffusion alone would allow.  This transport is powered by cellular metabolic processes, and allows transport to proceed in a locally ballistic manner.  However, these processes still have a length scale at which long-range order disappears, and in many cases they appear diffusive again.  This thesis explores transport in two example biological systems, looking at the interplay between directed transport and effective diffusion.

The first case under consideration is diffusion with confined geometries, through the lens of the Fluorescence Recovery After Photobleaching (FRAP) microscopy technique.  We create a computational model of the process, and use it to investigate the performance of analytical models in a series of common biological shapes.  Additionally, we confirm this model, by using it to identify the diffusion coefficient of secretory vesicles in the growing tip cells of the moss Physcomitrella Patens.  We find that highly confined geometries, such as the cell tip, break analytical models of diffusion, but that our computational approach remains usable for experimental analysis.

Our second system is the flagellar transport of spermatazoa.  This active swimming process is ballistic at short ranges, but, at sufficiently long length scales, transitions to being effectively diffusive.  We create a series of computational modeling approaches, bridging length and complexity scales, from detailed modeling of sperm movement using Multi-particle Collision Dynamics (MPCD), to a coarse-grained persistent random walk.  We then applied this model to microfluidic sperm-sorting devices, to address a clinical problem in male infertility.  Conventionally, sperm used for Assistive Reproductive Technologies are isolated using effective but potentially damaging methods, due to the use of a centrifuge, which we avoid by using a microfluidic device.  We find that the use of periodic post arrays in microfluidic channels can increase the effective diffusion coefficient for sperm, via persistence length enhancement.  When the results were implemented into a real device (SPARTAN, patent pending) device, we find that, within an unprecedentedly short 10 min assay time, we can achieve yields with over 99% motility of sorted sperm, a 5-fold improvement in morphology, 3-fold increase in nuclear maturity, and 24-fold enhancement in DNA integrity.

 

Committee Members:

Utkan Demirci

Erkan Tüzel

Luis Vidali

Qi Wen

Kun-Ta Wu