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Rational design of potent phosphopeptide binders to endocrine Snk PBD domain by integrating machine learning optimization, molecular dynamics simulation, binding energetics rescoring, and in vitro affinity assay.
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-11-29 DOI: 10.1007/s00249-024-01729-5
Zhaohui Wang, Jixiao Lan, Yan Feng, Yumei Chen, Meiyuan Chen

Human Snk is an evolutionarily conserved serine/threonine kinase essential for the maintenance of endocrine stability. The protein consists of a N-terminal catalytic domain and a C-terminal polo-box domain (PBD) that determines subcellular localization and substrate specificity. Here, an integrated strategy is described to explore the vast structural diversity space of Snk PBD-binding phosphopeptides at a molecular level using machine learning modeling, annealing optimization, dynamics simulation, and energetics rescoring, focusing on the recognition specificity and motif preference of the Snk PBD domain. We further performed a systematic rational design of potent phosphopeptide ligands for the domain based on the harvested knowledge, from which a few potent binders were also confirmed by fluorescence-based assays. A phosphopeptide PP17 was designed as a good binder with affinity improvement by 6.7-fold relative to the control PP0, while the other three designed phosphopeptides PP7, PP13, and PP15 exhibit a comparable potency with PP0. In addition, a basic recognition motif that divides potent Snk PBD-binding sequences into four residue blocks was defined, namely [Χ-5Χ-4]block1-[Ω-3Ω-2Ω-1]block2-[pS0/pT0]block3-[Ψ+1]block4, where the X represents any amino acid, Ω indicates polar amino acid, Ψ denotes hydrophobic amino acid, and pS0/pT0 is the anchor phosphoserine/phosphothreonine at reference residue position 0.

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引用次数: 0
Exploring characteristic features for effective HCN1 channel inhibition using integrated analytical approaches: 3D QSAR, molecular docking, homology modelling, ADME and molecular dynamics 利用综合分析方法探索有效抑制 HCN1 通道的特征:3D QSAR、分子对接、同源建模、ADME 和分子动力学。
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-11-03 DOI: 10.1007/s00249-024-01726-8
Shiwani Sharma, Priyanka Rana, Vijayta Dani Chadha, Neelima Dhingra, Tanzeer Kaur

Neuropathic pain (NP) is characterized by hyperalgesia, allodynia, and spontaneous pain. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel involved in neuronal hyperexcitability, has emerged as an important target for the drug development of NP. HCN channels exist in four different isoforms, where HCN1 is majorly expressed in dorsal root ganglion having an imperative role in NP pathophysiology. A specific HCN1 channel inhibitor will hold the better potential to treat NP without disturbing the physiological roles of other HCN isoforms. The main objective is to identify and analyze the chemical properties of scaffolds with higher HCN1 channel specificity. The 3D-QSAR studies highlight the hydrophobic & hydrogen bond donor groups enhance specificity towards the HCN1 channel. Further, the molecular interaction of the scaffolds with the HCN1 pore was studied by generating an open-pore model of the HCN1 channel using homology modelling and then docking the molecules with it. In addition, the important residues involved in the interaction between HCN1 pore and scaffolds were also identified. Moreover, ADME predictions revealed that compounds had good oral bioavailability and solubility characteristics. Subsequently, molecular dynamics simulation studies revealed the better stability of the lead molecules A7 and A9 during interactions and ascertained them as potential drug candidates. Cumulative studies provided the important structural features for enhancing HCN1 channel-specific inhibition, paving the way to design and develop novel specific HCN1 channel inhibitors.

神经病理性疼痛(NP)以痛觉减退、异动感和自发性疼痛为特征。超极化激活的环核苷酸门控(HCN)通道参与神经元的过度兴奋,已成为 NP 药物开发的一个重要靶点。HCN 通道有四种不同的异构体,其中 HCN1 主要在背根神经节中表达,在 NP 病理生理学中起着至关重要的作用。特异性 HCN1 通道抑制剂将具有更好的治疗 NP 的潜力,同时不会干扰其他 HCN 同工酶的生理作用。研究的主要目的是鉴定和分析具有更高 HCN1 通道特异性的支架的化学特性。3D-QSAR 研究强调疏水和氢键供体基团可增强对 HCN1 通道的特异性。此外,通过同源建模生成 HCN1 通道的开孔模型,然后将分子与之对接,研究了支架与 HCN1 孔的分子相互作用。此外,还确定了参与 HCN1 孔道与支架之间相互作用的重要残基。此外,ADME 预测显示,化合物具有良好的口服生物利用度和溶解度特性。随后的分子动力学模拟研究表明,先导分子 A7 和 A9 在相互作用过程中具有更好的稳定性,因此被确定为潜在的候选药物。累积研究提供了增强 HCN1 通道特异性抑制作用的重要结构特征,为设计和开发新型特异性 HCN1 通道抑制剂铺平了道路。
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引用次数: 0
Quantitative characterization of non-specific interaction of two globular proteins with Dextran T70 in a binary mixture 二元混合物中两种球状蛋白质与右旋糖酐 T70 非特异性相互作用的定量表征。
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-10-25 DOI: 10.1007/s00249-024-01727-7
Adedayo A. Fodeke

In a bid to quantify the contribution of molecular structure to non-specific interactions leading to functionally important structural changes in cellular processes, the self-interaction of dextran-T70 (DT70) and its interaction with each of bovine serum albumin (BSA) and ovomucoid trypsin inhibitor (OVO) were studied at pH 7.4 between 5 and 37 °C. The dependences of the apparent molecular weight of each of BSA, OVO and DT70 on the concentration of DT70 were independent of temperature. The activity coefficient of the interaction of each species on DT70 concentration was also independent of temperature. The change in activity coefficient was however dependent on the molecular structure and size of the interacting species. The energy of insertion of each macromolecule in DT70 increased in the order DT70 > BSA > OVO. These findings show that although the enthalpic contribution is negligible, the extent of the entropic contribution to the macromolecular activity coefficient of interaction is chiefly the consequence of the exclusion volume of the interacting macromolecules.

为了量化分子结构对导致细胞过程中重要功能结构变化的非特异性相互作用的贡献,我们研究了葡聚糖-T70(DT70)的自身相互作用以及它与牛血清白蛋白(BSA)和卵磷脂胰蛋白酶抑制剂(OVO)在 5 至 37 °C、pH 值为 7.4 的条件下的相互作用。BSA、OVO 和 DT70 的表观分子量与 DT70 的浓度无关。每种物质相互作用的活性系数对 DT70 浓度的影响也与温度无关。不过,活性系数的变化取决于相互作用物种的分子结构和大小。每种大分子在 DT70 中的插入能按照 DT70 > BSA > OVO 的顺序增加。这些发现表明,虽然焓贡献可以忽略不计,但熵对相互作用的大分子活性系数的贡献程度主要取决于相互作用的大分子的排阻体积。
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引用次数: 0
The origin of mutational epistasis 突变外显的起源
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-10-23 DOI: 10.1007/s00249-024-01725-9
Jorge A. Vila

The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin (molecular basis) of epistasis—the non-additive interactions between mutations—is still, nonetheless, unknown. The existence of a new perspective on protein folding, a problem that needs to be conceived as an ‘analytic whole’, will enable us to shed light on the origin of mutational epistasis at the simplest level—within proteins—while also uncovering the reasons why the genetic background in which they occur, a key component of molecular evolution, could foster changes in epistasis effects. Additionally, because mutations are the source of epistasis, more research is needed to determine the impact of post-translational modifications, which can potentially increase the proteome’s diversity by several orders of magnitude, on mutational epistasis and protein evolvability. Finally, a protein evolution thermodynamic-based analysis that does not consider specific mutational steps or epistasis effects will be briefly discussed. Our study explores the complex processes behind the evolution of proteins upon mutations, clearing up some previously unresolved issues, and providing direction for further research.

蛋白质折叠、突变、表观遗传和进化这些相互关联的过程,由于其对结构生物学和进化生物学的重要意义,多年来一直是广泛分析的主题。然而,表观遗传的起源(分子基础)--突变之间的非加性相互作用--至今仍是未知数。蛋白质折叠是一个需要被视为 "分析整体 "的问题,从这个新视角出发,我们将能够从最简单的层面--蛋白质内部--揭示突变表观效应的起源,同时揭示作为分子进化关键组成部分的遗传背景为何会促进表观效应的变化。此外,由于突变是表观性的来源,因此需要开展更多研究来确定翻译后修饰对突变表观性和蛋白质可进化性的影响,因为翻译后修饰有可能使蛋白质组的多样性增加几个数量级。最后,我们将简要讨论一种不考虑特定突变步骤或外显效应的基于热力学的蛋白质进化分析。我们的研究探索了突变后蛋白质进化背后的复杂过程,澄清了一些之前尚未解决的问题,为进一步的研究提供了方向。
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引用次数: 0
Time-dependent simulation of blood flow through an abdominal aorta with iliac arteries 随时间变化的腹主动脉与髂动脉血流模拟。
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-10-18 DOI: 10.1007/s00249-024-01724-w
Grzegorz Górski, Krzysztof Kucab

Atherosclerosis is one of the important diseases of the circulatory system because atherosclerotic plaques cause significant disruption of blood flow. Therefore, it is very important to properly understand these processes and skillfully simulate blood flow. In our work, we consider blood flow through an abdominal aorta with iliac arteries, assuming that the right iliac artery is narrowed by an atherosclerotic lesion. Blood flow is simulated using the laminar, standard (k-omega) and standard (k-epsilon) models. The obtained results show that despite the use of identical initial conditions, the distribution of velocity flow and wall shear stress depends on the choice of flow simulation model. For the (k-epsilon) model, we obtain higher values of speed and wall shear stress on atherosclerotic plaque than in the other two models. The laminar and (k-omega) models predict larger areas where reverse blood flow occurs in the area behind the atherosclerotic lesion. This effect is associated with negative wall shear stress. These two models give very similar results. The results obtained by us, and those reported in the literature, indicate that (k-omega) model is the most suitable for blood flow analysis.

动脉粥样硬化是循环系统的重要疾病之一,因为动脉粥样硬化斑块会严重破坏血流。因此,正确理解这些过程并巧妙地模拟血流非常重要。在我们的工作中,我们考虑了流经腹主动脉和髂动脉的血流,假设右髂动脉因动脉粥样硬化病变而狭窄。使用层流、标准 k - ω 和标准 k - ϵ 模型模拟了血流。结果表明,尽管使用了相同的初始条件,但血流速度和血流壁剪应力的分布取决于血流模拟模型的选择。对于 k - ϵ 模型,我们在动脉粥样硬化斑块上获得了比其他两个模型更高的速度和壁剪应力值。层流模型和 k - ω 模型预测在动脉粥样硬化病变后方的区域会出现较大的反向血流。这种效应与负壁剪应力有关。这两个模型得出的结果非常相似。我们获得的结果和文献报道的结果表明,k - ω 模型最适合用于血流分析。
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引用次数: 0
Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution 水溶液中小溶质二聚化过程中的极端焓熵补偿。
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-10-15 DOI: 10.1007/s00249-024-01722-y
David J. Scott, Donald J. Winzor

This communication summarizes findings from the earliest encounters with extreme enthalpy‒entropy compensation, a phenomenon first detected in the 1950s by a reappraisal of isopiestic and calorimetric measurements on aqueous urea solutions in terms of solute self-association. Because concurrent studies of carboxylic acid association were confined to measurement of the equilibrium constant by conductance, IR spectrophotometry or potentiometric titration measurements, temperature-independence of the dimerization constant was mistakenly taken to signify a value of zero for Δ(H^o) instead of (Δ(H^o) ‒ TΔ(S^o)). In those studies of small-solute self-association the extreme enthalpy‒entropy compensation was reflecting the action of water as a reactant whose hydroxyl groups were competing for the solute carbonyl involved in self-association. Such action gives rise to a positive temperature dependence of Δ(H^o) that could well be operating in concert with that responsible for the commonly observed negative dependence for protein‒ligand interactions exhibiting extreme enthalpy‒entropy compensation, where the solvent contribution to the energetics reflects changes in the extent of ordered water structure in hydrophobic environments.

这篇通讯总结了最早接触极端焓熵补偿的研究成果,这一现象最早是在 20 世纪 50 年代通过重新评估等焓法和热量测定法对尿素水溶液进行溶质自结合测量而发现的。由于当时对羧酸缔合的研究仅限于通过电导率、红外分光光度法或电位滴定法测量平衡常数,二聚常数与温度无关的特性被错误地认为表示 Δ H o 的值为零,而不是 (Δ H o - TΔ S o)。在这些关于小溶质自结合的研究中,极高的焓熵补偿反映了水作为反应物的作用,其羟基与参与自结合的溶质羰基竞争。这种作用导致了 Δ H o 的正温度依赖性,它很可能与通常观察到的蛋白质-配体相互作用的负温度依赖性一致,后者表现出极高的焓熵补偿,其中溶剂对能量的贡献反映了疏水环境中有序水结构程度的变化。
{"title":"Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution","authors":"David J. Scott,&nbsp;Donald J. Winzor","doi":"10.1007/s00249-024-01722-y","DOIUrl":"10.1007/s00249-024-01722-y","url":null,"abstract":"<div><p>This communication summarizes findings from the earliest encounters with extreme enthalpy‒entropy compensation, a phenomenon first detected in the 1950s by a reappraisal of isopiestic and calorimetric measurements on aqueous urea solutions in terms of solute self-association. Because concurrent studies of carboxylic acid association were confined to measurement of the equilibrium constant by conductance, IR spectrophotometry or potentiometric titration measurements, temperature-independence of the dimerization constant was mistakenly taken to signify a value of zero for Δ<span>(H^o)</span> instead of (Δ<span>(H^o)</span> ‒ TΔ<span>(S^o)</span>). In those studies of small-solute self-association the extreme enthalpy‒entropy compensation was reflecting the action of water as a reactant whose hydroxyl groups were competing for the solute carbonyl involved in self-association. Such action gives rise to a positive temperature dependence of Δ<span>(H^o)</span> that could well be operating in concert with that responsible for the commonly observed negative dependence for protein‒ligand interactions exhibiting extreme enthalpy‒entropy compensation, where the solvent contribution to the energetics reflects changes in the extent of ordered water structure in hydrophobic environments.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"373 - 384"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01722-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Application of artificial neural network for the mechano-bactericidal effect of bioinspired nanopatterned surfaces 应用人工神经网络研究生物启发纳米图案表面的机械杀菌效果。
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-10-07 DOI: 10.1007/s00249-024-01723-x
Ecren Uzun Yaylacı

This study aimed to calculate the effect of nanopatterns’ peak sharpness, width, and spacing parameters on P. aeruginosa and S. aureus cell walls by artificial neural network and finite element analysis. Elastic and creep deformation models of bacteria were developed in silico. Maximum deformation, maximum stress, and maximum strain values of the cell walls were calculated. According to the results, while the spacing of the nanopatterns is constant, it was determined that when their peaks were sharpened and their width decreased, maximum deformation, maximum stress, and maximum strain affecting the cell walls of both bacteria increased. When sharpness and width of the nano-patterns are kept constant and the spacing is increased, maximum deformation, maximum stress, and maximum strain in P. aeruginosa cell walls increase, but a decrease in S. aureus was observed. This study proves that changes in the geometric structures of nanopatterned surfaces can show different effects on different bacteria.

本研究旨在通过人工神经网络和有限元分析计算纳米图案的峰值锐度、宽度和间距参数对铜绿假单胞菌和金黄色葡萄球菌细胞壁的影响。在硅学中建立了细菌的弹性和蠕变变形模型。计算了细胞壁的最大变形、最大应力和最大应变值。结果表明,在纳米图案间距不变的情况下,当其峰值变尖、宽度变小时,两种细菌细胞壁的最大变形、最大应力和最大应变都会增加。当纳米图案的尖锐度和宽度保持不变且间距增大时,铜绿假单胞菌细胞壁的最大变形、最大应力和最大应变都会增加,但金黄色葡萄球菌的最大变形、最大应力和最大应变都会减少。这项研究证明,纳米图案表面几何结构的变化会对不同细菌产生不同的影响。
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引用次数: 0
Structural investigation, computational analysis, and theoretical cryoprotectant approach of antifreeze protein type IV mutants 抗冻蛋白 IV 型突变体的结构研究、计算分析和理论低温保护方法。
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-09-27 DOI: 10.1007/s00249-024-01719-7
Azadeh Eskandari, Thean Chor Leow, Mohd Basyaruddin Abdul Rahman, Siti Nurbaya Oslan

Antifreeze proteins (AFPs) have unique features to sustain life in sub-zero environments due to ice recrystallization inhibition (IRI) and thermal hysteresis (TH). AFPs are in demand as agents in cryopreservation, but some antifreeze proteins have low levels of activity. This research aims to improve the cryopreservation activity of an AFPIV. In this in silico study, the helical peptide afp1m from an Antarctic yeast AFP was modeled into a sculpin AFPIV, to replace each of its four α-helices in turn, using various computational tools. Additionally, a new linker between the first two helices of AFPIV was designed, based on a flounder AFPI, to boost the ice interaction activity of the mutants. Bioinformatics tools such as ExPASy Prot-Param, Pep-Wheel, SOPMA, GOR IV, Swiss-Model, Phyre2, MODFOLD, MolPropity, and ProQ were used to validate and analyze the structural and functional properties of the model proteins. Furthermore, to evaluate the AFP/ice interaction, molecular dynamics (MD) simulations were executed for 20, 100, and 500 ns at various temperatures using GROMACS software. The primary, secondary, and 3D modeling analysis showed the best model for a redesigned antifreeze protein (AFP1mb, with afp1m in place of the fourth AFPIV helix) with a QMEAN (Swiss-Model) Z score value of 0.36, a confidence of 99.5%, a coverage score of 22%, and a p value of 0.01. The results of the MD simulations illustrated that AFP1mb had more rigidity and better ice interactions as a potential cryoprotectant than the other models; it also displayed enhanced activity in limiting ice growth at different temperatures.

抗冻蛋白(AFP)具有抑制冰再结晶(IRI)和热滞后(TH)的独特功能,可在零度以下的环境中维持生命。抗冻蛋白作为低温保存剂的需求量很大,但有些抗冻蛋白的活性水平较低。这项研究旨在提高 AFPIV 的冷冻保存活性。在这项硅学研究中,利用各种计算工具将南极酵母 AFP 中的螺旋肽 afp1m 建模为 sculpin AFPIV,依次替换其四个 α-螺旋。此外,还以比目鱼 AFPI 为基础,在 AFPIV 的前两个螺旋之间设计了一个新的连接体,以提高突变体的冰相互作用活性。生物信息学工具如 ExPASy Prot-Param、Pep-Wheel、SOPMA、GOR IV、Swiss-Model、Phyre2、MODFOLD、MolPropity 和 ProQ 被用来验证和分析模型蛋白的结构和功能特性。此外,为了评估 AFP 与冰的相互作用,还使用 GROMACS 软件在不同温度下分别进行了 20、100 和 500 ns 的分子动力学(MD)模拟。一级、二级和三维建模分析表明,重新设计的抗冻蛋白(AFP1mb,用afp1m代替第四个AFPIV螺旋)的最佳模型的QMEAN(瑞士模型)Z分值为0.36,置信度为99.5%,覆盖率为22%,P值为0.01。MD 模拟结果表明,与其他模型相比,AFP1mb 作为一种潜在的冷冻保护剂具有更高的刚性和更好的冰相互作用;它在不同温度下限制冰生长的活性也有所增强。
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引用次数: 0
Computational study on the impact of linkage sequence on the structure and dynamics of lignin 连接序列对木质素结构和动力学影响的计算研究
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-09-19 DOI: 10.1007/s00249-024-01720-0
Derya Vural

Lignin, one of the most abundant biopolymers on Earth, is of great research interest due to its industrial applications including biofuel production and materials science. The structural composition of lignin plays an important role in shaping its properties and functionalities. Notably, lignin exhibits substantial compositional diversity, which varies not only between different plant species but even within the same plant. Currently, it is unclear to what extent this compositional diversity plays on the overall structure and dynamics of lignin. To address this question, this paper reports on the development of two models of lignin containing all guaiacyl (G) subunits with varied linkage sequences and makes use of all-atom molecular dynamics simulations to examine the impact of linkage sequence alone on the lignin’s structure and dynamics. This work demonstrates that the structure of the lignin polymer depends on its linkage sequence at temperatures above and below the glass transition temperature ((T_textrm{g})), but the polymers exhibit similar structural properties as it is approaching the viscous flow state (480 K). At low temperatures, both of lignin models have a local dynamics confined in a cage, but the size of cages varies depending on structural differences. Interestingly, at temperatures higher than (T_textrm{g}), the different linkage sequence leads to the subtle dynamical difference which diminishes at 480 K.

木质素是地球上最丰富的生物聚合物之一,由于其工业应用(包括生物燃料生产和材料科学)而备受研究关注。木质素的结构组成对其性质和功能的形成起着重要作用。值得注意的是,木质素表现出极大的成分多样性,不仅不同植物物种之间存在差异,甚至同一植物内部也存在差异。目前,还不清楚这种成分多样性在多大程度上影响了木质素的整体结构和动态。为了解决这个问题,本文报告了两种木质素模型的开发情况,这两种模型都包含具有不同连接序列的全部愈创木酰基(G)亚基,并利用全原子分子动力学模拟来研究仅连接序列对木质素结构和动力学的影响。这项研究表明,在高于和低于玻璃转化温度(T_textrm{g})时,木质素聚合物的结构取决于其连接序列,但在接近粘性流动状态(480 K)时,聚合物表现出相似的结构特性。在低温条件下,两种木质素模型都具有局限在笼子中的局部动力学特性,但笼子的大小因结构差异而不同。有趣的是,在温度高于(T_textrm{g})时,不同的连接序列导致了微妙的动力学差异,这种差异在 480 K 时逐渐减小。
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引用次数: 0
Physical aspects of epithelial cell–cell interactions: hidden system complexities 上皮细胞-细胞相互作用的物理方面:隐藏的系统复杂性
IF 2.2 4区 生物学 Q3 BIOPHYSICS Pub Date : 2024-09-10 DOI: 10.1007/s00249-024-01721-z
Ivana Pajic-Lijakovic, Milan Milivojevic, Peter V. E. McClintock

The maintenance of homeostasis and the retention of ordered epithelial cell self-organization are essential for morphogenesis, wound healing, and the spread of cancer across the epithelium. However, cell–cell interactions in an overcrowded environment introduce a diversity of complications. Such interactions arise from an interplay between the cell compressive and shear stress components that accompany increased cell packing density. They can lead to various kinds of cell rearrangement such as: the epithelial-to-mesenchymal cell state transition; live cell extrusion; and cell jamming. All of these scenarios of cell rearrangement under mechanical stress relate to changes in the strengths of the cell–cell and cell–matrix adhesion contacts. The objective of this review study is twofold: first, to provide a comprehensive summary of the biological and physical factors influencing the effects of cell mechanical stress on cell–cell interactions, and the consequences of these interactions for the status of cell–cell and cell–matrix adhesion contacts; and secondly, to offer a bio-physical/mathematical analysis of the aforementioned biological aspects. By presenting these two approaches in conjunction, we seek to highlight the intricate nature of biological systems, which manifests in the form of complex bio-physical/mathematical equations. Furthermore, the juxtaposition of these apparently disparate approaches underscores the importance of conducting experiments to determine the multitude of parameters that contribute to the development of these intricate bio-physical/mathematical models.

维持上皮细胞的平衡和保持有序的上皮细胞自组织对形态发生、伤口愈合和癌症在上皮细胞中的扩散至关重要。然而,在过度拥挤的环境中,细胞与细胞之间的相互作用会带来多种多样的并发症。这种相互作用源于伴随细胞堆积密度增加而产生的细胞压缩应力和剪切应力之间的相互作用。它们可导致各种细胞重排,如:上皮细胞向间质细胞状态的转变、活细胞挤压和细胞堵塞。所有这些机械应力下的细胞重排情况都与细胞-细胞和细胞-基质粘附接触强度的变化有关。本综述研究的目的有二:首先,全面总结影响细胞机械应力对细胞-细胞相互作用影响的生物和物理因素,以及这些相互作用对细胞-细胞和细胞-基质粘附接触状态的影响;其次,对上述生物方面进行生物物理/数学分析。通过将这两种方法结合起来介绍,我们试图突出生物系统错综复杂的性质,这种性质以复杂的生物物理/数学方程的形式表现出来。此外,将这些看似不同的方法并列在一起,突出了进行实验以确定有助于建立这些复杂的生物物理/数学模型的众多参数的重要性。
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引用次数: 0
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