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Dissertation Defense May 10th – Shayandev Sinha

Title: BILAYER MEMBRANE ELECTROSTATICS AND CHARGE-REGULATED MEMBRANE-NANOPARTICLE INTERACTIONS

Date: Thu, May 10, 2018

Time: 3:00 PM – 5:00 PM

Location: KEB 1105, Pepco Seminar Room, Jeong H. Kim Engineering Building

Committee members: 

Assistant Professor Siddhartha Das (Chair/Advisor)

Associate Professor Amir Riaz

Assistant Professor Ryan Sochol

Professor Abhijit Dasgupta

Associate Professor Liangbing Hu (Dean’s Representative)


Abstract:

The main aim of this thesis is to look into the influence of this ionic environment and the role that it can play on adhesion of nanoparticles. In order to look deeply we first look into the electrostatics of plasma membranes. We develop a continuum model to investigate the role of the ionic environment or the EDL on the electrostatics present across the membrane. This investigation led us to a very important aspect of membrane electrostatics. We found out charge-inversion like characteristics on the cytosol side (fluids present inside the cell) of the membrane. This was a breakthrough in the understanding of membrane electrostatics until today as there has been no reports of such charge inversion like characteristics in a monovalent ionic scenario. The next step to look into was how the surface charge density of the membrane and the concentration of the ions influence this electrostatics. This led to more interesting results. We found out that for biologically relevant conditions and for standard membrane surface charges, there is a possibility of having the location of charge inversion on the surface of the membrane itself. This is another interesting result as typically plasma membranes are negatively charged. An exploration of a domain phase-space where there can be a charge-inversion like behavior on the negatively charged membrane surface itself has been performed.

We then move on to explore the effect of this electrostatics on the adhesion of NP on the membranes. Most these adhesive processes happen through the ligand-receptor mechanism. Therefore, until and unless a ligand is able to physically influence a receptor and can get bonded to it the process of adhesion will never begin. The electrostatics can cause a hindrance to this phenomenon. The main reason is the osmotic pressure, which causes a repulsion between the ligand and the receptor present on the cell membrane. Through our analysis, we calculated such repulsion and calculated the distance up to which this repulsion remains strong. We hypothesize that if the length of the ligand-receptor complex is not larger than this zone of repulsion then the process of adhesion will not even begin. We then looked into membrane-NP adhesion process given that the ligand-receptor bond has taken place. In that case, we investigate the effects of the concentration of the ionic environment on the relative number of ligand-receptor bonds. We thus explore the domain of non-specific adhesion influencing cytotoxicity in cells.

Finally, we study the conditions by which one can resist non-specific adhesion by bilayer coated nanoparticles.