Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

Abstract

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/ d - phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

Chirality Effects in Peptide Assembly Structures

“…Left-handed matrix formed by L -phenylalanine derivative was conductive for osteogenic lineage, while right-handed matrix formed by its D -analog was conductive for adipogenic lineage ( Wei et al, 2019 ). These different regulatory effects on cells were suggested to be closely related to stereospecific interactions between peptide assemblies and proteins ( Dou et al, 2019 , 2020 ; Wei et al, 2019 ; Sun et al, 2021 ).…”

A chiral microenvironment promotes retinal progenitor cell proliferation by activating the Akt and ERK pathways

“…The separation of RPCs was performed as previously described. 17 Briefly, the retina was isolated from mice, digested with TrypLE Express Enzyme (Gibco™) at room temperature for 5 min, and cultured in Advanced DMEM/F12 (Invitrogen) supplemented with 20 ng mL −1 EGF (Invitrogen), a 1% N2 neural supplement (Invitrogen), and 2 mM l -glutamine (Invitrogen).…”

“…Immunofluorescence assays were performed by following a previously described protocol. 17 Briefly, RPCs were seeded in chiral nano-coated 24-well plates (5 × 10 4 cells per well). Three days later, RPCs were fixed with 4% paraformaldehyde, blocked with 10% goat serum, and incubated with primary antibodies (Ki-67, mouse monoclonal, BD, 1 : 200–1 : 100) at 4 °C overnight.…”

Herb‐Functionalized Chronic Wound Dressings for Enhancing Biological Functions: Multiple Flavonoids Coordination Driven Strategy

“…Moreover, the chiral microenvironment constructed by D/L-BA supramolecular hydrogelators in the hydrogel provided a chiral 3D extracellular matrix-mimicking microenvironment, which was beneficial to cell growth. [42,43,44] This phenomenon may be attributed to the suitable and noncovalent spatial interactions between proteins and M-chiral structures, which are essential to the coordinated movement of cells in the wound zones. Overall, the herb-functionalized hydrogels consisted of TF, chiral supramolecules, and polymers that were noncytotoxic and bioactive, which promotes vital steps in angiogenesis, including cell migration, angiogenesis, and tube formation.…”