Albumin-derived nanocarriers: substrates for enhanced cell adhesive ligand display and cell motility.
Albumin-derived nanocarriers: substrates for enhanced cell adhesive ligand display and cell motility.
复制标题
白蛋白衍生的纳米载体：增强细胞粘附配体展示和细胞运动的基质。
DOI：
10.1016/j.biomaterials.2006.02.007
复制
发表时间：
2006
期刊：
影响因子：
14
通讯作者：
Moghe,PrabhasV
中科院分区：
文献类型：
--
作者：
Sharma,RamI;Pereira,Marian;Schwarzbauer,JeanE;Moghe,PrabhasV
在纳米级合成生物材料上组织的细胞粘附配体可以潜在地再现细胞外基质的纳米级组织和细胞动力学的后续效应。在这项研究中，100 nm的白蛋白纳米载体（ANC）的制造，作为一个明确定义的配体，从纤连蛋白的重组片段组成的含RGD的模块10和含协同区域的模块9的纳米级组织单位。采用常规蛋白质缀合化学来制造具有增加水平的展示配体的纳米载体。与同等水平的吸附配体相比，发现吸附到基底上的配体官能化ANC的呈现增强角质形成细胞附着，这得到ELISA数据的支持，即ANC上配体的展示基本上增加了细胞结合结构域的可及性，并且AFM数据表明配体可能由于配体ANC排斥而暴露。ANC的配体呈递将细胞形态从静止表型转化为能动表型，表达丝状伪足样微延伸，并减少粘着斑，表明细胞粘附强度降低。因此，发现细胞运动性在配体-ANC底物上相对于具有等同水平配体的底物显著升高。总的来说，配体功能化的白蛋白纳米载体提供了一个独特的模型平台，具有两个不同的性质：增强的配体暴露，以增强细胞附着在低浓度的配体;和增强的细胞脱离，运动表型和迁移动力学。
Cell-adhesive ligands organized on nanoscale synthetic biomaterials can potentially recapitulate the nanoscale organization of extracellular matrix and the consequent effects of cell dynamics. In this study, 100nm albumin nanocarriers (ANC) were fabricated to serve as nanoscale organizational units for a well-defined ligand, the recombinant fragment from fibronectin comprised of the RGD-containing module 10 and the synergy-region-containing module 9. Conventional protein conjugation chemistry was employed to fabricate nanocarriers with increasing levels of displayed ligand. Presentation of ligand-functionalized ANCs adsorbed onto substrates was found to enhance keratinocyte attachment when compared to equivalent levels of adsorbed ligands, supported by ELISA data that the display of ligand on ANCs essentially increased the accessibility of the cell-binding domain and AFM data that the ligand was likely exposed due to ligand–ANC repulsion. The ligand presentation from ANCs converted the cellular morphology from a stationary phenotype to a motile phenotype, with the expression of filopodia-like microextensions, and a decrease in focal adhesions, indicating decreased cell adhesion strength. Consequently, cell motility was found to be significantly elevated on ligand–ANC substrates relative to substrates with equivalent levels of ligand. Overall, the ligand-functionalized albumin nanocarriers offer a unique model platform with two distinct properties: enhanced ligand exposure for enhancement of cell attachment to ligands at low concentrations; and enhanced cell detachment, motile phenotype, and migration kinetics.