Multiphase Mechanics of Tumor Encapsulation & Multilobulation

研究人员使用力学模型来研究肿瘤包膜、多叶形成和跨包膜扩散的机制。对于正常细胞、肿瘤细胞、它们所锚定的细胞外基质(ECM)以及它们所沐浴的间质液体，写出了质量和动量平衡方程。该系统由质量供应、偏应力张量和动量供应的适当本构关系封闭。前者是基于对肿瘤细胞生长的现象学观察，而后者是基于每个阶段的力学性质。模型方程由一组非线性守恒方程和演化方程组成，利用渐近分析、分歧分析和摄动理论对模型方程进行分析，以量化化学过程(如ECM的产生和降解)和组织的力学性质(如ECM密度和硬度)在影响包膜形成中的相对重要性。另一个目标是描述导致多叶形成的分叉。通过对模型的分析和模拟，研究人员旨在发现哪些因素(机械和化学)决定了成功的胶囊形成，并量化了它们的影响。肿瘤被包裹成连续的细胞或由结缔组织隔开的不同大小的几个叶的机制是肿瘤生物学中一个有趣的、重要的和尚未解决的现象。事实上，肿瘤周围致密包膜的存在(或不存在)是决定宿主预后和最终生存的主要因素。尽管胶囊的形成很重要，但人们对胶囊形成的过程知之甚少。研究人员开发了一个数学模型框架，基于所涉及的物理力和细胞相互作用描述肿瘤的生长、包膜、多叶形成和跨包膜扩散。其具体目的是使用力学模型来帮助理解i)肿瘤细胞、正常细胞和细胞外基质(ECM)相互作用在包膜形成中的作用，ii)肿瘤诱导的ECM的产生和降解对肿瘤包膜形成的影响，iii)组织属性如ECM密度和硬度在减缓或阻碍肿瘤包膜形成过程中的作用，以及iv)允许简单包膜的细胞连续体过渡到多结节形式的分叉。这对临床诊断和预后都有影响。

Jackson0114473 The investigator uses mechanical models to investigate themechanisms involved in tumor encapsulation, multiple lobeformation, and transcapsular spread. Mass and momentum balanceequations are written for the normal cells, neoplastic cells, theextracellular matrix (ECM) on which they are anchored, and theinterstitial fluid in which they are bathed. This system isclosed by suitable constitutive relations for the mass supply,the partial stress tensor, and the momentum supply of eachconstituent. The former is defined on the basis ofphenomenological observations of tumor cell growth and the latteris based on the mechanical properties of each phase. The modelequations, consisting of a set nonlinear conservation andevolution equations, are analyzed using asymptotic analysis,bifurcation analysis, and perturbation theory in order toquantify the relative importance of chemical processes (such asECM production and degradation) and mechanical properties of thetissue (such as ECM density and stiffness) in influencing capsuleformation. A further objective is to characterize thebifurcation that leads to multiple lobe formation. Throughanalysis and simulation of the model, the investigator aims todiscover which factors (mechanical and chemical) determinesuccessful capsule formation and to quantify their influence. The mechanisms by which a tumor becomes encapsulated as acontinuum of cells or as several lobes of different sizes,separated by connective tissue, is an interesting, important, andunsolved phenomenon in tumor biology. In fact, the presence (orabsence) of a dense capsule surrounding a neoplastic mass is amajor determinant of prognosis and the ultimate survival of thehost. Despite the importance of capsule formation, little isknown about the process by which capsules arise. Theincestigator develops a mathematical modeling framework thatdescribes tumor growth, encapsulation, multiple lobe formation,and transcapsular spread based on the physical forces andcellular interactions involved. The specific aims are to usemechanical models to assist in understanding i) the role tumorcell, normal cell, and extracellular matrix (ECM) interactions incapsule formation, ii) the effects of tumor induced ECMproduction and degradation on the formation of tumor capsules,iii) the role of tissue properties such as ECM density andstiffness in slowing or impeding the process of tumorencapsulation, and iv) the bifurcation that allows a simpleencapsulated continuum of cells to make the transition to amulti-nodular form. There are implications for clinical diagnosisas well as for prognosis.