Mesoporous Frameworks Assembled from Amphiphilic Collagen-Mimetic Peptides

The rational design of porous frameworks with defined pore dimensions and surface chemistry is a critical step toward their implementation in diverse applications. While traditional porous materials are typically constructed from abiotic components, there is increasing interest in using biologically derived building blocks (e.g., peptides and proteins) that offer un-matched structural and functional diversity. Here, we report the construction of crystalline mesoporous frameworks that are self-assembled from amphiphilic collagen-mimetic peptides (aCMPs). These aCMPs consist of charge-segregated collagen-mimetic peptides (CMPs) modified with lipid tails at their N-termini. Through hydrophobic and electrostatic interactions, aCMPs organize into extended, three-dimensional (3D) porous architectures. Comprehensive structural characterization using transmission electron microscopy (TEM), cryogenic TEM (cryo-TEM), and small/wide-angle x-ray scattering (SAXS/WAXS) reveals that these frameworks exhibit hexagonally arranged mesopores with diameters of approximately 3 nm. Circular dichroism (CD) spectroscopy indicates significant disruptions to the canonical collagen triple helix structure of the CMP domains, likely due to the packing of alkyl chains within hydrophobic cores. Notably, the crystal size and lattice packing parameters can be systematically tuned by varying the length of the lipid tail (C12, C10, C8), while shortening the chain further (to C6) leads to the emergent formation of nanosheets. These observations highlight the importance of balancing electrostatic and hydrophobic interactions to promote long-range order. Based on our findings, we propose a “hub and spoke” assembly model wherein hexagonally packed hydrophobic domains (“hubs”) are interconnected by antiparallel-aligned CMP domains (“spokes”), resulting in the observed supramolecular architecture. Overall, this work introduces a new class of mesoporous frameworks, derived from synthetically accessible, sequence-programmable peptide amphiphiles, representing a significant step forward in expanding the architectural footprint of peptide-based materials and their corresponding application potential.