Regulating the migration of smooth muscle cells by a vertically distributed poly(2-hydroxyethyl methacrylate) gradient on polymer brushes covalently immobilized with RGD peptides

Abstract

Cell migration is of paramount importance for the processes of tissue repair and regeneration. So far, the gradient localization of biological cues perpendicular to the substrate, which is the usual case for the biological signaling molecules to locate in ECM in vivo, has been scarcely studied, and has not been used to guide the directional migration of cells. In this study, we prepare a depth gradient of RGD peptides along the polymer chains, which is used to guide the directional migration of SMCs after a second hydrophilic bock is prepared in a gradient manner. For the first time the directional migration of SMCs is achieved under the guidance of a depth gradient of RGD ligands. The mechanisms of different cell migration abilities are further discussed based on the results of cell adhesion, cell adhesion force, cytoskeleton alignment and expression of relative proteins and genes. This work paves a new strategy by fabricating a gradient polymer brushes with immobilized bioactive molecules to dominate the directional cell migration, and elucidates the mechanisms underlining the biased migration along RGD depth localization gradients, shedding a light for the design of novel biomaterials to control and guide cell migration and invasion.

Selective Adhesion and Directional Migration of Endothelial Cells Guided by Cys‐Ala‐Gly Peptide Density Gradient on Antifouling Polymer Brushes

“…As Figure b shows, the C1s core‐level spectra were curve‐fitted into ester bonds (OCO) at 288.8 eV, carbon‐oxygen bonds (CO) at 286.4 eV, and saturated carbons (CC) at 284.8 eV. The peak area ratio of OCO, CO, and CC was calculated as 3:2.13:1, which is in between the theoretical value of PHEMA (3:2:1) and PGMA (3:3:1), revealing the successful copolymerization of GMA in the polymer brushes …”

“…Due to the hydrophobic nature of BES, significant increase of the static water contact angle from < 5° to 77.4 ± 0.7° was observed after the treatment. The thickness increase after the salinization process was measured to be ≈3 nm, which also revealed the success of initiator immobilization …”

“…As shown in Figure b, the surface content of CAG peptides increased along with the gradient position, indicating the successful generation of CAG peptide density gradient on the polymer brushes. It has to mention that most of the epoxy groups should have been reacted with the thiol groups, because the direct epoxy ring opening reaction is carried out in a spontaneous way and the reaction efficiency is also pretty high at an alkaline condition . Furthermore, the small amount of unreacted epoxy groups could be quenched quickly by the proteins and amino acids in the culture medium, which has no obvious effect on cell behaviors in this study (see the cell culture results: the adhesion of SMCs and ECs were inhibited effectively at 0 mm of the gradient with mPEG‐SH only).…”

Surfaces functionalized with hierarchical polymer brushes and their biomedical applications

“…交联在初始聚合的PAAm嵌段内实现, 而黏附肽RGD键 合到随后的PAA嵌段, 提供信号传递 [83] (网络版彩图) Figure 20 The biofunctional block-copolymer brush (PAAm/bi-sAAm-b-PAA) architecture. The crosslinking is implemented in the initially polymerized PAAm block, while the adhesion peptide RGD, conjugated to the subsequently polymerized PAA block, affords the signaling [83] 图 21 RGD肽梯度深度结构及其对细胞定向迁移的调节作 用. PHEMA厚度增加方向定义为"+X"方向 [84] (网络版彩图) Figure 21 Schematic illustration to show the structure of depth localization gradient of RGD peptides and its mediation of directional cell migration. The direction of increased PHEMA thickness is defined as "+X" direction [84] (color online).…”

Biodegradable small-diameter vascular graft: types of modification with bioactive molecules and RGD peptides

“…Контроль специфических взаимодействий между клеточными рецепторами и лигандами ЭЦМ является критическим аспектом в тканевой инженерии, так как обеспечивает эффективность клеточной миграции и адгезии [90]. Показано, что именно длина лиганда обеспечивает биодоступность RGD-пептидов для интегрин-опосредованного взаимодействия с клеткой и дальнейшей регуляции силы адгезии, скорости миграции [91]. Количество вариаций «полимерная композиция -линкер -RGD-пептид» достаточно велико, поэтому в настоящее время вопрос о приоритетном варианте модифицирования RGDпептидами полимерных сосудистых протезов открыт.…”