Casalini Tommaso, Rosolen Amanda, Henriques Carolina Yumi Hosoda, Perale Giuseppe
Polymer Engineering Laboratory, Department of Innovative Technologies, Institute for Mechanical Engineering and Materials Technology, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Front Bioeng Biotechnol. 2020 Jun 30;8:718. doi: 10.3389/fbioe.2020.00718. eCollection 2020.
Polymeric nanoparticles, which by virtue of their size (1-1000 nm) are able to penetrate even into cells, are attracting increasing interest in the emerging field of nanomedicine, as devices for, e.g., drugs or vaccines delivery. Because of the involved dimensional scale in the nanoparticle/cell membrane interactions, modeling approaches at molecular level are the natural choice in order to understand the impact of nanoparticle formulation on cellular uptake mechanisms. In this work, the passive permeation across cell membrane of oligomers made of two employed polymers in the biomedical field [poly-D,L-lactic acid (PDLA) and poly(3-hydroxydecanoate) (P3HD)] is investigated at fundamental atomic scale through molecular dynamics simulations. The free energy profile related to membrane crossing is computed adopting umbrella sampling. Passive permeation is also investigated using a coarse-grained model with MARTINI force field, adopting well-tempered metadynamics. Simulation results showed that P3HD permeation is favored with respect to PDLA by virtue of its higher hydrophobicity. The free energy profiles obtained at full atomistic and coarse-grained scale are in good agreement each for P3HD, while only a qualitative agreement was obtained for PDLA. Results suggest that a reparameterization of non-bonded interactions of the adopted MARTINI beads for the oligomer is needed in order to obtain a better agreement with more accurate simulations at atomic scale.
聚合物纳米颗粒因其尺寸（1 - 1000纳米）甚至能够穿透细胞，在新兴的纳米医学领域作为例如药物或疫苗递送的载体正吸引着越来越多的关注。由于纳米颗粒/细胞膜相互作用涉及的尺寸尺度，分子水平的建模方法是理解纳米颗粒制剂对细胞摄取机制影响的自然选择。在这项工作中，通过分子动力学模拟在基本原子尺度上研究了生物医学领域中两种常用聚合物[聚-D,L-乳酸（PDLA）和聚（3-羟基癸酸）（P3HD）]制成的低聚物跨细胞膜的被动渗透。采用伞形采样计算与跨膜相关的自由能分布。还使用具有MARTINI力场的粗粒化模型，采用加权直方图动力学研究被动渗透。模拟结果表明，由于其较高的疏水性，P3HD的渗透比PDLA更有利。在全原子尺度和粗粒化尺度上获得的P3HD自由能分布彼此吻合良好，而对于PDLA仅获得了定性的吻合。结果表明，为了与原子尺度上更精确的模拟获得更好的吻合，需要对所采用的MARTINI珠子对低聚物的非键相互作用进行重新参数化。
