INM-Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.
Max Planck Graduate Center, Forum Universitatis 2, Building 1111, 55122, Mainz, Germany.
Chembiochem. 2018 Jun 18;19(12):1271-1279. doi: 10.1002/cbic.201800118. Epub 2018 May 15.
Neuro-regeneration after trauma requires growth and reconnection of neurons to reestablish information flow in particular directions across the damaged tissue. To support this process, biomaterials for nerve tissue regeneration need to provide spatial information to adhesion receptors on the cell membrane and to provide directionality to growing neurites. Here, photoactivatable adhesive peptides based on the CASIKVAVSADR laminin peptidomimetic are presented and applied to spatiotemporal control of neuronal growth to biomaterials in vitro. The introduction of a photoremovable group [6-nitroveratryl (NVOC), 3-(4,5-dimethoxy-2-nitrophenyl)butan-2-yl (DMNPB), or 2,2'-((3'-(1-hydroxypropan-2-yl)-4'-nitro-[1,1'-biphenyl]-4-yl)azanediyl)bis(ethan-1-ol) (HANBP)] at the amino terminal group of the K residue temporally inhibited the activity of the peptide. The bioactivity was regained through controlled light exposure. When used in neuronal culture substrates, the peptides allowed light-based control of the attachment and differentiation of neuronal cells. Site-selective irradiation activated adhesion and differentiation cues and guided seeded neurons to grow in predefined patterns. This is the first demonstration of ligand-based light-controlled interaction between neuronal cells and biomaterials.
创伤后的神经再生需要神经元的生长和重新连接,以在受损组织中重新建立特定方向的信息流。为了支持这个过程,用于神经组织再生的生物材料需要为细胞膜上的粘附受体提供空间信息,并为生长的神经突提供方向性。在这里,提出了基于 CASIKVAVSADR 层粘连蛋白肽模拟物的光活化粘附肽,并将其应用于体外生物材料中神经元生长的时空控制。在 K 残基的氨基末端基团中引入光可去除基团[6-硝基香草醛(NVOC)、3-(4,5-二甲氧基-2-硝基苯基)丁-2-基(DMNPB)或 2,2'-((3'-(1-羟基丙烷-2-基)-4'-硝基-[1,1'-联苯]-4-基)氮杂二基)双(乙-1-醇)(HANBP)]暂时抑制了肽的活性。通过受控光暴露恢复了生物活性。当用于神经元培养底物时,这些肽允许基于光控制神经元细胞的附着和分化。选择性照射激活了粘附和分化线索,并引导接种的神经元以预定的模式生长。这是首次证明神经元细胞和生物材料之间基于配体的光控相互作用。