סמינר מיוחד בפיזיקה של מערכות ביולוגיות וחומרים רכים

Biomolecular Condensates: Nature’s Physical Computer

David G. Lynn

Across all domains of life, intrinsically disordered proteins form coacervates known as biomolecular condensates (BMC) that maintain a dynamic superposition of entangled conformational states. Environmental inputs can nucleate distinct assemblies from this ensemble that provide functional feedback for adaptation. The physical computation enabling precise output couples the digital information in the genome to analog environments in real time, impacting both acute and global adjustments. The human brain is supported by an extracellular matrix, a BMC, that provides dynamic structural and acute signaling support for cellular adaptation and memory. We will discuss how this matrix both sustains neurogenesis and propagates disease in the human brain. We will further discuss the development of an alternate dynamic collagen polymerization network to complement and extend the natural physical computation in human brain organoids.

Biomolecules for non-biological things: Peptide ‘Bundlemer’ design for model nanoparticle creation and hierarchical solution assembly

Darrin J. Pochan

A solution-assembled system comprised of computationally designed coiled coil bundle motifs, also known as ‘bundlemers’, will be discussed as model colloidal nanoparticle systems for the formation of hierarchical materials. The molecules and nanostructures are non-natural amino acid sequences and provide opportunities for controlled solution behavior and arbitrary nanostructure creation with peptides. With control of the display of the amino acid side chains (both natural and non-natural) throughout the peptide bundles, desired physical and covalent (through appropriate ‘click’ chemistry) interactions are designed to control interparticle interactions in solution, which involve both individual bundlemer particles as well as polymers of connected bundlemers. With proper design of individual bundlmer particles, two target nanomaterials are being created.  First, interbundlemer end-to-end stacking is observed between particles through physical interactions to form lyotropic liquid crystal phases. Important for liquid crystal formation is the design of single charge bundlemer particles (e.g., with only positive/basic amino acids) that lack of opposite charges on the particle surfaces so that there are no attractive electrostatic patches to disrupt the LC alignment. The liquid crystal phases span nematic to hexagonal columnar to smectic depending on peptide concentration as well as on specific peptide design (e.g., number of negative or positive charges, spatial display of charge, amino acid type to create charge). Second, nanoporous lattices can be formed through simply solution mixing.  The lattices display crystalline-like structure but with regular pores on the nanoscale.  The lattice structures are formed through two different assembly mechanisms; the functionalization of bundlemer paritcles with hydrophobic side chains on their exterior for lattice formation through interparticle hydrophobic interactions or through the mixing of oppositely charged, single charged bundlemers through electrostatic complexation.  Included in the discussion will be new, single charge peptide molecule design, hierarchical assembly pathway design, control of nanostructure, and characterization with cryotransmission electron micorscopy, transmission electron microscopy, small-angle x-ray scattering, and molecular dynamics simulations.