Neuronal Growth on l- and d-Cysteine Self-Assembled Monolayers Reveals Neuronal Chiral Sensitivity

Abstract

Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of L-and D-cysteine on single neuronal growth. L-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with L-and D-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via the thiol groups, the neuronal membrane was exposed to the molecular chiral site. Thus, our results have demonstrated high neuronal chiral sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells and providing a reference for studying chiral drugs.

Engineering Cell Surface Glycans with Carbohydrate Enantiomers to Alter Bacterial Binding and Adhesion

“…The ability of biomolecules to distinguish between D and L configurations is crucial in all biological events, including cell‐cell, cell‐proteins and cell‐bacterial interactions . Nearly all mammalian lectins prefer the D‐form over the L‐form of carbohydrates, the exceptions to this is L‐fucose and L‐iduronic acids.…”

“…The ability of biomolecules to distinguish between D and L configurations is crucial in all biological events, including cellcell, cell-proteins and cell-bacterial interactions. [1][2][3][4][5][6][7] Nearly all mammalian lectins prefer the D-form over the L-form of carbohydrates, the exceptions to this is L-fucose and L-iduronic acids. L-fucose is found in mammalian cell surfaces in the form of Lewis x/a -and sialyl Lewis x/a -carbohydrates and are pivotal ligands for C-type and selectin lectins.…”

Chiral Biomaterials: From Molecular Design to Regenerative Medicine

“…These surface‐associating immune cells were less adherent, anchored poorly, and showed lower levels of activity on the d ‐enantiomer surface than the l ‐enantiomer surface. Chiral effects impinge on neuronal growth, and a study showed that l ‐cysteine reduced neuronal growth and prevented attachment; by contrast, d ‐cysteine facilitated growth and attachment . Consequently, polymer surface chirality affects the cell fate mediated via protein adsorption characteristics together with its own display of chirality .…”

Chiral Selective Transport of Proteins by Cysteine‐Enantiomer‐Modified Nanopores

“…[1][2][3][4] Chirality is an intriguing and intrinsic feature of life and is extensively found in most biomolecular components of living organisms,s uch as DNA, proteins,p hospholipids,a nd sugars. [9][10][11][12][13] Nevertheless, whether chirality influences the translocation behavior of proteins remains unclear.T herefore,itisofgreat importance to investigate the fundamental question:h ow chirality influences the protein transport process? [9][10][11][12][13] Nevertheless, whether chirality influences the translocation behavior of proteins remains unclear.T herefore,itisofgreat importance to investigate the fundamental question:h ow chirality influences the protein transport process?…”

“…[5][6][7][8] Accumulating evidence has indicated that most biological and physiological processes involve intermolecular interactions that are mediated by chirality. [9][10][11][12][13] Nevertheless, whether chirality influences the translocation behavior of proteins remains unclear.T herefore,itisofgreat importance to investigate the fundamental question:h ow chirality influences the protein transport process?…”