摘要
单分子运动追踪是研究软物质体系尤其是生命体系动力学过程和分子相互作用的重要方法,但如何理解生命体系中单分子运动行为的复杂性仍是一个巨大的挑战.针对这一问题,本工作提出了一种可对单分子轨迹进行高效识别和分类的、基于无监督学习的“两步归类法”:首先利用熵约束最小二乘法对扩散轨迹的受限程度进行区分,继而通过统计检验将非受限轨迹划分为亚扩散、正常扩散和超扩散等不同运动模式类型.利用该方法,本工作解析了DOPC模型细胞膜和活细胞膜内的单分子扩散运动特征,揭示了胆固醇成分对二者的差异影响.结果显示:模型膜和活细胞膜均包含多种不同的扩散模式;在DOPC模型膜体系中,胆固醇成分会阻碍膜内的分子扩散运动,且阻碍程度与胆固醇含量正相关;在活细胞体系中,分子运动速率显著低于模型膜体系,并且,胆固醇的去除会进一步减慢分子扩散速率.本研究有助于从单分子运动角度深入理解生物分子运动行为的复杂性及其对体系环境的依赖性.
Single molecular tracking is a valuable approach to investigate the dynamic processes and molecular interactions in soft matter systems,particularly in biological systems.However,understanding the complexity of single molecule motion behaviors in biological systems remains a significant challenge.To address this issue,we propose a two-step classification method based on unsupervised learning to efficiently identify and classify single molecule trajectories.Firstly,we employ an entropy-constrained least square method to distinguish between confined(e.g.,immobile)and unconfined diffusion trajectories.Subsequently,statistical tests are utilized to categorize the unconfined trajectories into different diffusion modes such as sub-diffusion,normal diffusion,and super-diffusion.By applying this method,we analyze the diffusion motion of single molecules in both DOPC model cell membranes and living cell membranes while uncovering their distinct responses to cholesterol composition.Our findings demonstrate that both model membranes and living cell membranes exhibit diverse molecular diffusion modes.Specifically,in the DOPC model mem-brane system,the presence of cholesterol components impedes lipid diffusion within the membrane.The degree of inhibition is positively correlated with the amount of cholesterol present.For instance,as the cholesterol content in the membrane increases from 0 to 20%(DOPC:Chol=4∶1)and 50%(DOPC:Chol=1∶1),there is an increase in the proportion of molecules,exhibiting confined diffusion and sub-diffusion(from 55%to 45%),while there is a decrease in the proportion of molecules,displaying normal diffusion and super-diffusion(from 45%to 35%).The ensemble diffusion coefficient of molecules in the membrane significantly decreases,which can be attributed to both a decrease in velocity among fast-moving molecules.Interestingly,after using MeβCD to remove cholesterol,the single-molecule mobility within the DOPC/Chol composite membrane system is restored to a level similar to that of the pure DOPC membrane.Conversely,in the living cell membrane system,the diffusion coefficient values of molecules are significantly lower than those observed in the model membrane system;furthermore,the removal of cholesterol further slows down the molecular diffusion rate.This study contributes to understanding the intricacies of biomolecular motility and its dependence on environmental factors from a perspective of single molecular motion.
作者
谭金鹏
张婉婷
徐成
卢雪梅
朱文圣
杨恺
元冰
Tan Jin-Peng;Zhang Wan-Ting;Xu Cheng;Lu Xue-Mei;Zhu Wen-Sheng;Yang Kai;Yuan Bing(School of Mathematics and Statistics,Northeast Normal University,Changchun 130024,China;Songshan Lake Materials Laboratory,Dongguan 523808,China;Center for Soft Condensed Matter Physics and Interdisciplinary Research,School of Physical Science and Technology,Soochow University,Suzhou 215006,China;School of Optical and Electronic Information,Suzhou City University,Suzhou 215104,China;Jiangsu Key Laboratory of Frontier Material Physics and Devices,Suzhou City University,Suzhou 215006,China)
出处
《物理学报》
SCIE
EI
CAS
CSCD
北大核心
2024年第18期278-288,共11页
Acta Physica Sinica
基金
国家自然科学基金(批准号:12274307,32230063,12347102,22307090,22203059)
广东省基础与应用基础研究基金(批准号:2023A1515011610)
江苏省自然科学基金(批准号:BK20210100)
前沿材料物理与器件省高校重点实验室(苏州大学)(批准号:KJS2131)资助的课题。
关键词
单分子运动
无监督学习
模型细胞膜
胆固醇
single molecular motion
unsupervised learning
model cell membrane
cholesterol
