Jadhav Sameer, Eggleton Charles D, Konstantopoulos Konstantinos
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
Curr Pharm Des. 2007;13(15):1511-26. doi: 10.2174/138161207780765909.
Cell adhesion plays a pivotal role in diverse biological processes that occur in the dynamic setting of the vasculature, including inflammation and cancer metastasis. Although complex, the naturally occurring processes that have evolved to allow for cell adhesion in the vasculature can be exploited to direct drug carriers to targeted cells and tissues. Fluid (blood) flow influences cell adhesion at the mesoscale by affecting the mechanical response of cell membrane, the intercellular contact area and collisional frequency, and at the nanoscale level by modulating the kinetics and mechanics of receptor-ligand interactions. Consequently, elucidating the molecular and biophysical nature of cell adhesion requires a multidisciplinary approach involving the synthesis of fundamentals from hydrodynamic flow, molecular kinetics and cell mechanics with biochemistry/molecular cell biology. To date, significant advances have been made in the identification and characterization of the critical cell adhesion molecules involved in inflammatory disorders, and, to a lesser degree, in cancer metastasis. Experimental work at the nanoscale level to determine the lifetime, interaction distance and strain responses of adhesion receptor-ligand bonds has been spurred by the advent of atomic force microscopy and biomolecular force probes, although our current knowledge in this area is far from complete. Micropipette aspiration assays along with theoretical frameworks have provided vital information on cell mechanics. Progress in each of the aforementioned research areas is key to the development of mathematical models of cell adhesion that incorporate the appropriate biological, kinetic and mechanical parameters that would lead to reliable qualitative and quantitative predictions. These multiscale mathematical models can be employed to predict optimal drug carrier-cell binding through isolated parameter studies and engineering optimization schemes, which will be essential for developing effective drug carriers for delivery of therapeutic agents to afflicted sites of the host.
细胞黏附在血管动态环境中发生的多种生物过程中起着关键作用，包括炎症和癌症转移。尽管细胞黏附过程复杂，但自然界中进化出的允许细胞在血管中黏附的过程可被利用来将药物载体导向靶细胞和组织。流体（血液）流动在中尺度上通过影响细胞膜的力学响应、细胞间接触面积和碰撞频率来影响细胞黏附，在纳米尺度上则通过调节受体 - 配体相互作用的动力学和力学来影响细胞黏附。因此，阐明细胞黏附的分子和生物物理本质需要一种多学科方法，该方法涉及将流体动力学流动、分子动力学和细胞力学的基本原理与生物化学/分子细胞生物学相结合。迄今为止，在识别和表征参与炎症性疾病以及在较小程度上参与癌症转移的关键细胞黏附分子方面已取得了重大进展。原子力显微镜和生物分子力探针的出现推动了纳米尺度水平上确定黏附受体 - 配体键的寿命、相互作用距离和应变响应的实验工作，尽管我们目前在这一领域的知识还远不完整。微吸管抽吸试验以及理论框架提供了有关细胞力学的重要信息。上述每个研究领域的进展都是建立细胞黏附数学模型的关键，这些模型纳入了适当的生物学、动力学和力学参数，从而能够进行可靠的定性和定量预测。这些多尺度数学模型可用于通过孤立参数研究和工程优化方案来预测最佳药物载体 - 细胞结合，这对于开发有效的药物载体以将治疗剂递送至宿主患病部位至关重要。
