Nuclear Pore Complex and Chromatin
This research is mainly concerned with the biopolymers that support life and the biomimetic materials inspired by them. A major theme is to understand the functional structure of intrinsically disordered proteins that mediate the biomass exchange between cell nucleus and cytoplasm via the nuclear pore complex. We have developed a molecular theory that explicitly takes into account the molecular conformations, electrostatics, hydrophobic interaction, excluded volume effect and acid-base equilibrium at a properly coarse-grained level, which allows a systematic study of the effect of polymer sequence on the gating function of the polymer-coated nanopores. We are interested in learning design principles from our model to guide the rational design of smart artificial nanopores based on sequence-controlled synthetic polymers, a novel nanomaterial aiming to deliver solutions to real-world problems such as water desalination, drug delivery, and energy conversion.
Inside the interphase cell nucleus, DNA, the macroscopically long biopolymer that carries our genomic information, is compacted into chromatin, whose 3D folding is associated with proper gene expression and misfolding with diseases. Chromatin structure exhibits many exotic properties that are alien to the common sense of polymer physics. We have developed a topological model for DNA folding to pivot a wide array of key chromatin features. We work with our experimental collaborators to provide fundamental insights into the relation between genomic interactions, chromatin heterogeneity, and transcription polarization, based on which understanding new strategy to fight cancer can be developed.
Protein Adsorption
One of the major projects that our group has been working in the last few years relates to the general problem of understanding the driving forces for protein adsorption and how to find mechanisms that enable the control of the adsorption process. For example, surfaces of biomaterials need to be protected from protein adsorption since this is the first step in the triggering of immunological responses by the body.
To this end we developed a general theoretical framework that enables us to study the thermodynamics and kinetics of protein adsorption. This is a particularly challenging problem since the time scale for the adsorption process may be in the hours. Our theoretical framework enables us to predict quantitatively the adsorption isotherms of lysozyme and fibrinogen on surfaces with grafted polyethylene oxide and we have described the mechanism by which grafted polymer layers prevent/reduce protein adsorption.
We are using our understanding of the kinetics of adsorption and desorption to propose surface modifiers that can be used in the design of controlled release devices. We are continuing our attempt to understand the link between detailed molecular organization and protein adsorption. To this end we are using detailed atomistic simulations the role of water on the protein-surface interactions.
Responsive Polymer Layers
Some types of polymer molecules can change their average properties as a response to changes in the environment. For example, thermoresponsive polymers collapse upon changes of temperature; polyelectrolytes change stretch upon changes in the ionic strength of the solution. We are modeling the behavior of a variety of responsive polymer systems in which the chain molecules are end-tethered to a surface or an interface. For example, in collaboration with the experimental group of Prof. J. Genzer, we are studying the ability of thermoresponsive polymers to adsorbed nanoparticles upon changes in temperature. A very important fundaments question that we aim to answer studying this family of systems is what is the coupling between the conformational degrees of freedom of the chains, the local density, the electrostatic interactions and the possibility of shifting the charge of the polymer segments through changes in the external conditions.
