[Amath-seminars] Jan. 19 - Special AMATH Seminar - Jay Newby (UNC)

Ulrich Hetmaniuk hetmaniu at uw.edu
Thu Jan 14 07:57:18 PST 2016

Dear All,

We hope you can join us for our special AMATH seminar on Tuesday January

Speaker: Jay Newby, University of North Carolina
Time: January 19th, 16h00
Location: DEM 004

Title: How first passage time problems can help us understand transport of
biomolecules in crowded environments


My talk will explore how first passage time problems are used to model
molecular transport in biology. Cellular environments are typically crowded
and highly heterogeneous. Even if large molecular species are not directly
involved in a given reaction, they can influence it through steric
interactions. By modeling the random motion of individual molecules in
heterogeneous environments, first passage time statistics can be used to
understand the dynamics of complex physiological processes. I will discuss
two examples.

(i) First, I will show how antibodies are dynamically tuned to anchor large
nanoparticles, such as viruses, to constitutive elements of a mucin polymer
gel. Mucus is a vital component of our immune system and provides a first
line of defense against infection. Large nanoparticles such as bacteria are
trapped within the tangled polymer network, preventing contact with the
mucus membrane and subsequent infection. However, some nanoparticles, such
as certain viruses, are small enough that they can freely diffuse through
the polymer matrix. One hypothesis for how smaller nanoparticles could be
trapped is that they are crosslinked to the mucin network by antibodies.
Indeed, antibodies are present in large quantities within mucus. However,
the hypothesis was previously discounted because antibodies typically have
very weak affinity for mucin. Counter to the prevailing theory that
antibodies are only effective if they have strong affinity to mucin, I will
show how weak affinity and rapid binding kinetics substantially improves
their ability to trap large nanoparticles.

(ii) In the second half of my talk I will present theoretical support for a
hypothesis about cell-cell contact, which plays a critical role in immune
function. A fundamental question for all cell-cell interfaces is how
receptors and ligands come into contact, despite being separated by large
molecules, the extracellular fluid, and other structures in the glycocalyx.
The cell membrane is a crowded domain filled with large glycoproteins that
impair interactions between smaller pairs of molecules, such as the T cell
receptor and its ligand, which is a key step in immunological information
processing and decision-making. A first passage time problem allows us to
gauge whether a reaction zone can be cleared of large molecules through
passive diffusion on biologically relevant timescales. I combine numerical
and asymptotic approaches to obtain a complete picture of the first passage
time, which shows that passive diffusion alone would take far too long to
account for experimentally observed cell-cell contact formation times. The
result suggests that cell-cell contact formation may involve previously
unknown active mechanical processes.

Speaker webpage
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