Computational and Theoretical Soft Matter

What is common between the genome carrying genetic information, and the plastic materials all around you, from water bottles to car bumpers? These “soft-matter’’ systems are composed of polymers, namely (relatively) long molecules with complex and diverse chemical structures. Polymeric matter, whether they are the constituents of a biological or a man-made system, can respond to external stimuli on the order of thermal fluctuations, such as mechanical stress, electric field, flow, pH level, or temperature, etc., and also, can transiently adapt geometrical constraints. While this versatility, on one hand, provides unprecedented survival and evolutionary capabilities for life, on the other hand, create new opportunities to design next-generation materials and pharmaceutical solutions.

bunch_of_DNAResearch in our lab focuses on fundamental problems in biology and materials sciences, on which we have currently either none or limited understanding.  Specifically, we study the kinetic and stimuli-responsive properties of synthetic and biological polymeric systems. Some examples are polyelectrolyte hydrogels’ mechanical and electric response or kinetics of protein-DNA interactions, and their role in chromatin organization, just to name a few. In our investigations, we use Molecular Dynamics (MD) simulations both on atomistic and coarse-grained levels, along with analytical tools of statistical mechanics.

Research Highlights

Facilitated disassociation of proteins from single binding sites

The standard picture of biomolecular interactions posits that the residence time (off rate) of transcription factors  (TFs) on DNA molecules in cells is independent of their concentration in solution. We designed and performed single-molecule experiments and simulations, where we measured dissociation kinetics of Fis (factor for inversion stimulator) – a key TF in E. coli bacteria and also major bacterial nucleoid protein — from single dsDNA binding sites. We find that the residence times (i.e., inverse off-rates of disassociation events) saturate at large protein concentrations in solution. While spontaneous (i.e., no unbound proteins in solution) dissociation shows a strong salt dependence, the facilitated dissociation depends only weakly on salt. A theoretical model  quantitatively explain our findings successfully and show the prevalence of this phenomenon. Read more on PNAS.

Co-Assembly of Peptide Amphiphiles (PAs) and Lipids into Supramolecular Nanostructures

Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. Examples include co-assembly of bioactive and nonbioactive molecules to modify the intensity of smart drugs, or functional biomimetic structures. In our work, the self-assembly of peptide amphiphiles (PAs) and fatty acids (lipids) driven primarily by anion−π interactions are focused. With a low content of the lipid, the cylindrical nanofiber morphology is preserved. However, as the aromatic units are placed along the peptide backbone away from the hydrophobic residues, the interactions with the lipids transform the cylindrical supramolecular morphology into ribbon-like structures. Increasing the stoichiometric ratio of the lipid to PA leads to either the formation of large spherical vesicles in the binary systems or a heterogeneous mixture of assemblies. Our findings reveal that specific inter-molecular interactions can drastically change supramolecular morphology and bridge between nano to micro scales. Read more on JACS.

 Electrostatic energy conversion with polyelectrolyte gels

amlccd_v004i008Apart, from being the main constituent of contact lenses and pill capsules, hydrogels have also proven themselves pretty effective in other applications including as mechano-electric energy converters or bio-mimetic structures.  The hydrogels own their special stimuli-responsive properties to their inherent electrostatic and elastic properties.  Their electrostatic nature allows them to adjust their internal interactions reversibly upon application of external stimuli such as electromagnetic fields or mechanical deformations.   Our MD simulations with explicit counterions showed that if a polyelectrolyte gel undergoes strain-control deformations, applied mechanical energy is mainly converted into electrostatic energy rather than other energy components (i.e., elastic and steric energies). The energetic change is due to the decreasing translational entropy of counterion gas trapped inside the gel in combination with chain elasticity of PE gels. This scenario is only possible if ionized counterions cannot vacate the gel, which is ensured by the local electro-neutrality condition. Read more on ACS Macro Letters.