Presenter: Dr. Elena F. Koslover, Ph.D., University of California, San Diego
Transport, Delivery, and Kinetics in Tubular Organelle Networks
Eukaryotic cells contain several organelle structures, including mitochondria and the endoplasmic reticulum (ER), that form interconnected networks of hollow tubules permeating the cell's interior. The ER plays a crucial role in cell functions ranging from protein quality control to calcium signaling. All these functions require luminal and membrane proteins to move within the networked architecture in order to find their binding partners. We leverage theoretical models and simulations, combined with analysis of live-cell imaging data, to investigate the transport of particles confined within reticulated network structures such as those found in mitochondria and the ER. We have developed new methods for efficient numerical simulations of particle motion over a network, for exact calculations of diffusive mean first passage times, and for analysis of dynamic experimental data such as single-particle trajectories and dynamic spreading of photoactivated probes.
Our work highlights the importance of tubular network connectivity in speeding diffusion-limited kinetics. We leverage results from percolation theory to establish a scaling behavior for global search times as a function of total edge length and loop number in a network. Furthermore, we establish that the spatial distribution of target sites, such as the ER exit sites for secretory proteins, can modulate search rates. Dispersion of targets over the network is shown to be more efficient than simply localizing targets in the region of protein production, providing a functional explanation for the prevalence of peripheral ER exit sites. We then proceed to develop a robust analysis method for characterizing the diffusion of membrane proteins on ER tubules and demonstrate evidence of non-diffusive motion for luminal proteins. Finally, we will discuss the limitations imposed by diffusive transport on ER functions such as localized calcium release, implicating a critical functional role for luminal super-diffusion.
Short Bio:
The Koslover research group studies transport and mechanics inside the complex, dynamic world of a living cell. We develop and implement analytical and computational techniques, coupled with analysis of live-cell imaging data from collaborating groups, to understand how intracellular components are harnessed for biological function. Elena Koslover completed her Ph.D. in biophysics as a Hertz Fellow at Stanford University, working in the Spakowitz research group on problems of DNA mechanics and genome packaging. Afterwards, she worked as a J.S. McDonnell Postdoctoral Research Fellow in the Theriot laboratory at Stanford, exploring organelle dynamics in motile cells. As a faculty member in the UCSD Physics Department, she is collaborating with cell biology research groups around the world to explore how complex intracellular geometries and organelle interactions modulate intracellular transport.
http://koslover.ucsd.edu/
