The laminin-1 sequence IKVAV-bearing peptide amphiphiles (PA) that self-assemble into nano-fibers upon the change of pH or salt addition has been shown to promote regeneration of both motor and sensory fibers in a mouse model of spinal cord injury. However, the process of the self-assembly is not known, and this has proven to be a hindrance in understanding how this system functions. We studied the self-assembly of PAs into cylindrical nanofibers using atomistic and coarse-grained molecular dynamics (CG MD) simulations. The PA for these studies includes a hydrophobic alkyl chain that is attached to the N-terminus of the sequence SLSLAAAEIKVAV. For the atomistic simulation, even though each PA has an identical sequence, a broad distribution of secondary structure in the PAs is found. The �-sheet population for the SLSL and IKV segments of the peptide is ~25 %, which is consistent with previous circular dichroism. The secondary structure obtained from the atomistic MD simulations was used as an input condition for the subsequent CG MD simulations. For CG MD simulations, we have studied the self-assembly of PAs into a cylindrical micelle fiber starting from a homogeneous mixture of PAs in water. Nine independent 16 �s runs all show spontaneous fiber formation in which the PA molecules first form spherical micelles, and then micelles form a three- dimensional network via van der Waals interactions. As the hydrophobic core belong to the different micelles merge, the three-dimensional network disappears and a fiber having a diameter of ~80 � appears. About 66 % of the surface of fiber is covered with the IKVAV epitope, and ~92 % of the epitope is exposed to water molecules. The structure of PA fibers and their self-assembly process in this work will be useful for designing new PA fibers that have potentially improved biological activities and functions.

Theoretical model of IKVAV epitope bearing peptide amphiphiles that promote neurite growth

245th National Meeting (2013)

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