Warren James P, Culbert Matthew P, Miles Danielle E, Maude Steven, Wilcox Ruth K, Beales Paul A
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
School of Mechanical Engineering, University of Leeds, Leeds LS2 9JT, UK.
Gels. 2023 May 26;9(6):441. doi: 10.3390/gels9060441.
Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation. Electrostatic repulsion is tuned by altering the peptide's net charge, and intermolecular attractions are controlled through the degree of hydrogen bonding between specific amino acid residues. We find that an overall net peptide charge of +/-2 is optimal to facilitate the assembly of self-supporting hydrogels. If the net peptide charge is too low then dense aggregates form, while a high molecular charge inhibits the formation of larger structures. At a constant charge, altering the terminal amino acids from glutamine to serine decreases the degree of hydrogen bonding within the assembling network. This tunes the viscoelastic properties of the gel, reducing the elastic modulus by two to three orders of magnitude. Finally, hydrogels could be formed from glutamine-rich, highly charged peptides by mixing the peptides in combinations with a resultant net charge of +/-2. These results illustrate how understanding and controlling self-assembly mechanisms through modulating intermolecular interactions can be exploited to derive a range of structures with tuneable properties.
自组装肽是一种很有前景的生物材料，在医疗器械和药物递送方面具有潜在应用。在合适的条件组合下，自组装肽可以形成自支撑水凝胶。在此，我们描述了平衡分子间吸引力和排斥力对于成功形成水凝胶至关重要。通过改变肽的净电荷来调节静电排斥力，并且通过特定氨基酸残基之间的氢键程度来控制分子间吸引力。我们发现肽的整体净电荷为+/-2最有利于促进自支撑水凝胶的组装。如果肽的净电荷过低，则会形成致密聚集体，而高净电荷会抑制更大结构的形成。在电荷恒定的情况下，将末端氨基酸从谷氨酰胺改变为丝氨酸会降低组装网络内的氢键程度。这调节了凝胶的粘弹性，使弹性模量降低两到三个数量级。最后，通过将富含谷氨酰胺、高电荷的肽以净电荷为+/-2的组合混合，可以形成水凝胶。这些结果说明了如何通过调节分子间相互作用来理解和控制自组装机制，从而获得一系列具有可调性质的结构。
