Loren Hough

Bound-State Diffusion due to Binding to Flexible Polymers in a Selective Biofilter.

Anonymous — Tue, 31 Dec 2019 17:43:30 +0000

Bound-State Diffusion due to Binding to Flexible Polymers in a Selective Biofilter. Anonymous (not verified) Tue, 12/31/2019 - 10:43

Selective biofilters are used by cells to control the transport of proteins, nucleic acids, and other macromolecules. Biological filters demonstrate both high specificity and rapid motion or high flux of proteins. In contrast, high flux comes at the expense of selectivity in many synthetic filters. Binding can lead to selective transport in systems in which the bound particle can diffuse, but the mechanisms that lead to bound diffusion remain unclear. Previous theory has proposed a molecular mechanism of bound-state mobility based only on transient binding to flexible polymers. However, this mechanism has not been directly tested in experiments. We demonstrate that bound mobility via tethered diffusion can be engineered into a synthetic gel using protein fragments derived from the nuclear pore complex. The resulting bound-state diffusion is quantitatively consistent with theory. Our results suggest that synthetic biological filters can be designed to take advantage of tethered diffusion to give rapid, selective transport.

Off

Traditional

White

Design principles of selective transport through biopolymer barriers

Anonymous — Wed, 23 Oct 2019 17:25:52 +0000

Design principles of selective transport through biopolymer barriers Anonymous (not verified) Wed, 10/23/2019 - 11:25

In biological systems, polymeric materials block the movement of some macromolecules while allowing the selective passage of others. In some cases, binding enables selective transport, while in others the most inert particles appear to transit most rapidly. To study the general principles of filtering, we develop a model motivated by features of the nuclear pore complex (NPC) which are highly conserved and could potentially be applied to other biological systems. The NPC allows selective transport of proteins called transport factors which transiently bind to disordered, flexible proteins called FG Nups. While the NPC is tuned for transport factors and their cargo, we show that a single feature is sufficient for selective transport: the bound-state motion resulting from transient binding to flexible filaments. Interchain transfer without unbinding can further improve selectivity, especially for crosslinked chains. We generalize this observation to model nanoparticle transport through mucus and show that bound-state motion accelerates transport of transient nanoparticle application, even with clearance by mucus flow. Our model provides a framework to control binding-induced selective transport in bipolymeric materials.

Off

Traditional

White

Scientist develops a new way to look at a cellular shapeshifter

Anonymous — Fri, 21 Oct 2016 06:00:00 +0000

Scientist develops a new way to look at a cellular shapeshifter Anonymous (not verified) Fri, 10/21/2016 - 00:00

BioFrontiers

Tubulin, a protein found in your cells, quietly lends itself to many life processes. It sorts itself into long chains, forming tubes that provide scaffolding for living cells. A versatile shapeshifter, tubulin can arrange itself into different structures during different types of cell behavior. Tubulin gained prominence for medical applications when Taxol, a chemical first found in the bark of the Pacific Yew tree, was developed as a treatment for ovarian, breast and lung cancers. Taxol binds to tubulin and makes it hard for the tubes to grow and shrink, preventing cancer cells from proliferating.

“Tubulin is one molecule that does many things in cells,” says Assistant Professor of Physics, Loren Hough, a member of the BioFrontiers Institute. “We're trying to understand how tubulin can play so many different roles."

Hough is focused on the ends of tubulin molecules, called the C-terminal tails. These tails coat the surfaces of the microtubules formed by tubulin. He is studying, in part, how much influence these tails exert on tubulin and its behavior. To answer some of the mysteries of tubulin, Hough developed a method to probe the C-terminal tails of tubulin using nuclear magnetic resonance spectroscopy, or NMR.

Hough wanted to measure how tubulin C-terminal tails influence cellular processes, but to do NMR he had to figure out how to get specific atoms into them first, as part of the isotopic labeling process. These atoms are easy to incorporate into bacteria, but tubulin cannot be made in bacteria because bacteria lack the suite of proteins that help tubulin fold into its correct shape. Hough brought in a helper: Tetrahymena thermophila. This small but mighty protozoan is common in freshwater ponds and is used frequently as a model organism in biological research. As it turns out, bacteria are a favorite snack of Tetrahymena, so Hough incorporated the isotopes into the bacteria, which were then devoured by the Tetrahymena. With the isotopes digested by the Tetrahymena, Hough was at last able to see the C-terminal tails in action using NMR, as described in a paper recently published in ACS Chemical Biology.

“There is beautiful physics regarding tubulin in general,” says Hough. “I thought the C-terminal tails might be affecting what we know about tubulin from a biophysical perspective. We think tubulin tails are like a knob the cell uses to control different features, but we don't know how the tails are used for this tuning. It’s exciting to be tackling these questions.”

Hough was awarded a New Investigator Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health this year to further the research in his lab. This grant, from the National Institute of General Medical Science, is meant to support the work of young faculty. Hough’s $1.8 million MIRA grant will run five years.

“The MIRA is great. It’s going to give our lab the ability to push this project forward, as well as other research on disordered proteins,” says Hough. “We’re looking forward to taking this work on tubulin C-terminal tails even further over the next five years.”

The Hough lab is part of the physics department's Biophysics group. At the University of ŷ��ڱ��Ƶ BioFrontiers Institute, researchers from the life sciences, physical sciences, computer science and engineering are working together to uncover new knowledge at the frontiers of science and partnering with industry to make their discoveries relevant.

Off

Traditional

White