Vasudevan Saranya, Chattaraj Sandipan, Enrico Alessandro, Pasqualini Francesco Silvio
Synthetic Physiology Lab, Department of Civil Engineering and Architecture, University of Pavia, Pavia 27100, Italy.
Langmuir. 2025 Feb 18;41(6):3852-3864. doi: 10.1021/acs.langmuir.4c03966. Epub 2025 Feb 6.
Hyaluronic acid (HA) is a nonsulfonated glycosaminoglycan critical in tissue development, physiology, and disease processes. To develop biomimetic in vitro models based on HA, it is important to understand the interaction of this polymer in its pristine form and with physiological solvents. However, atomistic simulations of HA chains are computationally challenging, especially when studying interactions with salts. To tackle this challenge, this study combined quantum mechanical (QM) calculations and molecular dynamics (MD) simulations to investigate HA's structure and behavior. This multiscale approach balances accuracy and computational efficiency. QM calculations emphasize the role of weak noncovalent hydrogen bonds in stabilizing d-glucuronic acid with N-acetyl-d-glucosamine. MD results show that more HA layers lead to a larger structure, higher water sensitivity, and increased dynamic and interlayer complexity. Our QM and MD simulations shed light on the structural dynamics and interactions of HA polymers and HA hydrogels, aiding in their design and optimization for biomedical applications and bridging computational and experimental approaches.
透明质酸（HA）是一种非磺化糖胺聚糖，在组织发育、生理学和疾病过程中起着关键作用。为了开发基于HA的仿生体外模型，了解这种聚合物在其原始形式下以及与生理溶剂的相互作用非常重要。然而，HA链的原子模拟在计算上具有挑战性，尤其是在研究与盐的相互作用时。为了应对这一挑战，本研究结合量子力学（QM）计算和分子动力学（MD）模拟来研究HA的结构和行为。这种多尺度方法平衡了准确性和计算效率。QM计算强调了弱非共价氢键在稳定d-葡萄糖醛酸与N-乙酰-d-葡萄糖胺中的作用。MD结果表明，更多的HA层会导致更大的结构、更高的水敏感性以及增加的动力学和层间复杂性。我们的QM和MD模拟揭示了HA聚合物和HA水凝胶的结构动力学和相互作用，有助于它们在生物医学应用中的设计和优化，并弥合计算和实验方法之间的差距。
