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

Ulrich Hetmaniuk hetmaniu at uw.edu
Mon Jan 18 20:10:26 PST 2016

Here is a kind reminder about Jay Newby's talk, Tuesday Jan. 19th at 16h00
(DEM 004).


Dear All,


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

> 19th.


> 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


> Abstract

> -----------


> 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

> ------------------------

> http://www.math.utah.edu/~newby/


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