Polymers and Parkinson’s: Elucidating Protein Function through Soft Matter Paradigms and Techniques

Polymers and Parkinson’s: Elucidating Protein Function through Soft Matter Paradigms and Techniques
Peter Chung, University of Chicago
Dr. Peter Chung
Date and time: Tue, Mar 10, 2020 - 11:30am
Refreshments at 11:15am
Location: LGRT 1033
Category: Condensed Matter Seminar
Special notes:

Please note unusual day -- Tuesday.

Abstract:

Despite being unequivocally linked to Parkinson’s disease, the function of a-synuclein remains unclear beyond transiently binding to the lipid membrane of synaptic vesicles (organelles filled with neurotransmitters). This is due, in part, to its intrinsically disordered nature; a-synuclein does not fold into a globular structure and instead behaves much like a biopolymer. While precluding traditional characterization methods, this makes a-synuclein incredibly amenable to investigation via a polymer physics framework. First, through purpose-designed membrane nanoparticles and advanced synchrotron X-ray methods I will demonstrate that a-synuclein binds to and collectively interacts to sterically-stabilize membrane surfaces, a biological manifestation of polyelectrolyte-stabilized colloids. I will then reconcile observed transient binding to synaptic vesicles by establishing that a-synuclein preferentially binds to osmotically-stressed membranes (a proxy for neurotransmitter-filled synaptic vesicles), a newly discovered biophysical function by which a-synuclein interrogates organelle contents. Utilizing these insights, I will contextualize a-synuclein as a guidepost that spatiotemporally directs non-equilibrium synaptic vesicles, a conferred function uniquely possible through its polymeric properties.