Effect Of Solvent Selectivity On Crystallization-driven Fibril Growth Kinetics Of Diblock Copolymers

In recent years,the demands of Alzheimer's disease treatment have been growing.It's widely believed that the misfolding of beta-amyloid protein results in the fibril growth for oligomers and fibers in vivo.These amyloid fibers tangle easily and come into the amyloid plaques,which block the information transfer between nerves,then lead to the Alzheimer's disease.Beta-amyloid protein is akin to the multi-block copolymer,which have alternative variation of block's hydrophilicity.The amyloid fiber contains a crystalline core of those hydrophobic residual groups,surrounded with the amorphous shell of those hydrophilic residual groups.Hence,the fibril growth is under nano-confinement of those amorphous blocks,giving rise to a cylindrical shape of the amyloid protein rather than the lamellar shape of polyamides.Thus,we use computer simulations to research the kinetics of di-block copolymers'crystallization-driven fibril self-assembly in dilute solutions,expecting to make some progress for develepment of clinical medicine and the treatment of Alzheimer's disease.We performed dynamic Monte Carlo simulations based on lattice model to investigate how the selective solvents on two blocks can influence the growth rate of fibril crystals in dilute solutions with the template induction.We changed the interactions between different blocks and solvent respectively.Then we find that the growth rate of the fibril crystals is accelerated when the interaction between crystalline block and the solvent becomes more positive,which means the crystalline block is more hydrophobic.On the other side,if the amorphous block is changed to be hydrophobic,the crystal growth will be slowed down.We use different mechanisms to explain the two phenomena:the former is due to the thermodynamic effect and the latter is owing to the shielding effect.Our research can contribute to the kinetics analysis of the di-block copolymers' nano-confined crystallization and the development of drug discovery for the Alzheimer's disease.