Abstract
Gradients of bioactive molecules play a crucial role in various biological processes like vascularization, tissue regeneration, or cell migration. To study these complex biological systems, it is necessary to control the concentration of bioactive molecules on their substrates. Here, we created a photochemical strategy to generate gradients using amyloid-like fibrils as scaffolds functionalized with a model epitope, that is, the integrin-binding peptide RGD, to modulate cell adhesion. The self-assembling β-sheet forming peptide (CKFKFQF) was connected to the RGD epitope via a photosensitive nitrobenzyl linker and assembled into photoresponsive nanofibrils. The fibrils were spray-coated on glass substrates and macroscopic gradients were generated by UV-light over a centimeter-scale. We confirmed the gradient formation using matrix-assisted laser desorption ionization mass spectroscopy imaging (MALDI-MSI), which directly visualizes the molecular species on the surface. The RGD gradient was used to instruct cells. In consequence, A549 adapted their adhesion properties in dependence of the RGD-epitope density.
Highlights
IntroductionConcentration gradients in the physiochemical environment of the extra cellular matrix (ECM) play a crucial role for cell adhesion and growth.[1,2] Gradual alterations of biochemical signals are the driving force for events like directed cell migration, that is, during nerve- and skin regeneration, vascularization, and immune responses.[3,4] Since these cellmaterial interactions occur at the mesoscopic length scale, and the ECM is composed of a dense network of fibrillar structures,[5−8] self-assembling peptides that form fibrils are promising biomaterials serving as scaffolds for cellular growth, adhesion, spreading and migration.[9,10]Amyloid-forming peptides are a special group of peptides assembling into highly ordered fibrils with a characteristic cross β-sheet structure and characteristic physical properties such as long-term stability in physiological environments, mechanical stiffness, and strong adhesion to various substrates.[11]
The fibril-forming sequence was extended at the N-terminus by a photocleavable nitrobenzyl linker (PCL) to connect bioactive epitopes to the surface of the nanofibrils
We developed an easy and fast strategy to create bioactive spatial gradients by spray-coating UV-sensitive, epitope functionalized amyloid-like peptide fibrils on glass slides
Summary
Concentration gradients in the physiochemical environment of the extra cellular matrix (ECM) play a crucial role for cell adhesion and growth.[1,2] Gradual alterations of biochemical signals are the driving force for events like directed cell migration, that is, during nerve- and skin regeneration, vascularization, and immune responses.[3,4] Since these cellmaterial interactions occur at the mesoscopic length scale, and the ECM is composed of a dense network of fibrillar structures,[5−8] self-assembling peptides that form fibrils are promising biomaterials serving as scaffolds for cellular growth, adhesion, spreading and migration.[9,10]Amyloid-forming peptides are a special group of peptides assembling into highly ordered fibrils with a characteristic cross β-sheet structure and characteristic physical properties such as long-term stability in physiological environments, mechanical stiffness, and strong adhesion to various substrates.[11]. Many amyloid-forming peptides exhibit intrinsic bioactivity and have recently evolved from a class exclusively associated with pathology[12,13] to functional materials[14,15] with applications, such as stimulating nerve growth for tissue engineering[16−18] and increased retroviral cell uptake for gene therapy.[19,20] In
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