NANOPORES AND NUCLEAR PORE COMPLEXES
with Martin Kröger, Yitzhak Rabin, and Igal Szleifer
We studied the structure of polymer layers end-grafted to the inner surface of nanopores, using Self Consistent Field. Our systematic study revealed how nanoconfinement affects the conformations of the polymer chains.
O. Peleg et al. [Featured on Cover] Biol. Chem.(2010)
MORPHOLOGY CONTROL OF HAIRY NANOPORES
The properties of polymer layers end-grafted to the inner surface of nanopores connected to solvent reservoirs are studied theoretically as a function of solvent quality and pore geometry. Our systematic study reveals that nanoconfinement is affected by both pore radius and length and that the conformations of the polymer chains strongly depend on their grafting position along the nanopore and on the quality of the solvent. In poor solvent, polymer chains can collapse to the walls, form a compact plug in the pore, or self-assemble into domains of different shape due to microphase separation. The morphology of these domains (aggregates on pore walls or stacked micelles along the pore axis) is mainly determined by the relationship between chain length and pore radius. In other cases the number of aggregates depends on pore length. The presence of reservoirs decreases confinement at pore edges due to the changes in available volume and introduces new organization strategies not available for infinite nanochannels. In good solvent conditions, chains grafted at the pore entrances stretch out of the pore, relieving the internal osmotic pressure and increasing the entropy of the polymers.
Our results show the complex interplay between the different interactions in a confined environment and the need to develop theoretical and experimental tools for their study.
Peleg et al., ACS Nano (2011)
EFFECT OF CHARGE, HYDROPHOBICITY, AND SEQUENCE OF NUCLEOPORINS ON THE TRANSLOCATION OF MODEL PARTICLES THROUGH THE NUCLEAR PORE COMPLEX
The molecular structure of the yeast nuclear pore complex (NPC) and the translocation of model particles have been studied with a molecular theory that accounts for the geometry of the pore and the sequence and anchoring position of the unfolded domains of the nucleoporin proteins (the FG-Nups), which control selective transport through the pore. The theory explicitly models the electrostatic, hydrophobic, steric, conformational, and acid-base properties of the FG-Nups. The electrostatic potential within the pore, which arises from the specific charge distribution of the FG-Nups, is predicted to be negative close to pore walls and positive along the pore axis. The positive electrostatic potential facilitates the translocation of negatively charged particles, and the free energy barrier for translocation decreases for increasing particle hydrophobicity. These results agree with the experimental observation that transport receptors that form complexes with hydrophilic/neutral or positively charged proteins to transport them through the NPC are both hydrophobic and strongly negatively charged. The molecular theory shows that the effects of electrostatic and hydrophobic interactions on the translocating potential are cooperative and nonequivalent due to the interaction-dependent reorganization of the FG-Nups in the presence of the translocating particle. The combination of electrostatic and hydrophobic interactions can give rise to complex translocation potentials displaying a combination of wells and barriers, in contrast to the simple barrier potential observed for a hydrophilic/neutral translocating particle. This work demonstrates the importance of explicitly considering the amino acid sequence and hydrophobic, electrostatic, and steric interactions in understanding the translocation through the NPC.
M. Tagliazucchi and O. Peleg et al., PNAS (2013)