Although the relationship between molecular and supramolecular chirality remains elusive,the existing results have demonstrated the vital role of hydrophilic motifs in controlling the supramolecular handedness of pept...Although the relationship between molecular and supramolecular chirality remains elusive,the existing results have demonstrated the vital role of hydrophilic motifs in controlling the supramolecular handedness of peptide nanofibrils compared with hydrophobic ones.However,unlike conventional hydrophobic residues,we speculate that aromatic hydrophobic residues are mostly likely to play a unique role in regulating the supramolecular handedness because theπ–πstacking interactions of their side chains are directional like hydrogen bonding and can direct high levels of self-assembly due to the geometric confining of aromatic rings.To confirm this hypothesis,we here design a series of amphiphilic short peptides,with their hydrophobic motifs being composed of aromatic residues.Their short lengths not only favor their structural stability,synthesis,and sequence variation but also enable us to readily link their molecular and supramolecular structures.Through the combination of experiments and theoretical simulations,we demonstrate that the peptides containing L-form aromatic residues form left-handed nanofibrils while those containing D-form aromatic residues assemble into right-handed ones,irrespective of the chirality of their C-terminal hydrophilic residue.Theoretical calculations revealed that the stacking of aromatic side chains betweenβ-strands directed the twisting direction of theβ-sheets formed,with L-and D-form phenylalanine side chains stacking in a clockwise and anti-clockwise way,and more ordered and stronger aromatic stacking for homochiral peptides facilitated the formation of nanofibrils with a marked tubular feature.This study has bridged the knowledge gap in our understanding of how aromatic residues affect the supramolecular chirality of short peptides.展开更多
Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetyl...Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetylcholine secretion by the vagal nerve, acid-base concentration, and tissue temperature) on cardiac pacemaker function and conduction were studied. Our results show that these two groups of mutations have different effects on pacemaker function and conduction. Furthermore, we found that the negative effects of these mutations could be altered by external stimuli. The bradycardic effects of mutations were magnified by an increase in acetylcholine level. Changes in acid-base concentration and tissue temperature increased the ability of the SAN to recover its pacemaker function. The results of this study increase our understanding of sodium channel disorders, and help to advance research on the treatment of these conditions.展开更多
Hydrogels resulting from the self-assembly of small peptides are smart nanobiomaterials as their nanostructuring can be readily tuned by environmental stimuli such as pH,ionic strength and temperature,thereby favoring...Hydrogels resulting from the self-assembly of small peptides are smart nanobiomaterials as their nanostructuring can be readily tuned by environmental stimuli such as pH,ionic strength and temperature,thereby favoring their practical applications.This work reports experimental observations of formation of peptide hydrogels in response to the redox environment.Ac-I 3 K-NH 2 is a short peptide amphiphile that readily self-assembles into long nanofibers and its gel formation occurs at concentrations of about 10 mmol/L.Introduction of a Cys residue into the hydrophilic region leads to a new molecule,Ac-I 3 CGK-NH 2,that enables the formation of disulfide bonds between self-assembled nanofibers,thus favoring cross-linking and promoting hydrogel formation.Under oxidative environment,Ac-I 3 CGK-NH 2 formed hydrogels at much lower concentrations(even at 0.5 mmol/L).Furthermore,the strength of the hydrogels could be easily tuned by switching between oxidative and reductive conditions and time.However,AFM,TEM,and CD measurements revealed little morphological and structural changes at molecular and nano dimensions,showing no apparent influence arising from the disulfide bond formation.展开更多
The aim of this study is to build two mathematical models of canine ionic currents specific to right atria and left atria.The canine left atria mathematical model was firstly modified from the Ramirez-Nattel-Courteman...The aim of this study is to build two mathematical models of canine ionic currents specific to right atria and left atria.The canine left atria mathematical model was firstly modified from the Ramirez-Nattel-Courtemanche(RNC) model using the recently available experimental data of ionic currents and was further developed based on our own experimental data.A model of right atria was then built by considering the differences between right atria and left atria.The two developed models well reproduced the experimental data on action potential morphology,the rate dependence,and action potential duration restitution.They are useful for investigating the mechanisms underlying the het-erogeneity of canine regional action potentials and would help the simulation of whole heart excitation propagation and cardiac arrhythmia in the near future.展开更多
基金the National Natural Science Foundation of China(Nos.22172193,22072181,and U1832108)a joint Innovate UK-Syngenta funded project under knowledge transfer partnership(No.KTP12697)an EPSRC IAA 377 grant(No.R128362)with Arxada.We acknowledge the use of the resources of the China Spallation Neutron Source in Dongguan of Guangdong Province of China.
文摘Although the relationship between molecular and supramolecular chirality remains elusive,the existing results have demonstrated the vital role of hydrophilic motifs in controlling the supramolecular handedness of peptide nanofibrils compared with hydrophobic ones.However,unlike conventional hydrophobic residues,we speculate that aromatic hydrophobic residues are mostly likely to play a unique role in regulating the supramolecular handedness because theπ–πstacking interactions of their side chains are directional like hydrogen bonding and can direct high levels of self-assembly due to the geometric confining of aromatic rings.To confirm this hypothesis,we here design a series of amphiphilic short peptides,with their hydrophobic motifs being composed of aromatic residues.Their short lengths not only favor their structural stability,synthesis,and sequence variation but also enable us to readily link their molecular and supramolecular structures.Through the combination of experiments and theoretical simulations,we demonstrate that the peptides containing L-form aromatic residues form left-handed nanofibrils while those containing D-form aromatic residues assemble into right-handed ones,irrespective of the chirality of their C-terminal hydrophilic residue.Theoretical calculations revealed that the stacking of aromatic side chains betweenβ-strands directed the twisting direction of theβ-sheets formed,with L-and D-form phenylalanine side chains stacking in a clockwise and anti-clockwise way,and more ordered and stronger aromatic stacking for homochiral peptides facilitated the formation of nanofibrils with a marked tubular feature.This study has bridged the knowledge gap in our understanding of how aromatic residues affect the supramolecular chirality of short peptides.
基金supported by the National Natural Science Foundation for Theoretical Physics of China (11047017)the Wellcome Trust (081808/Z/06/Z)+1 种基金the Biotechnology and Biological Sciences Research Council (BBS/B1678X), UKthe Special Foundation of Education of Anhui Province for Excellent Young Scientists (2011SQRL023)
文摘Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetylcholine secretion by the vagal nerve, acid-base concentration, and tissue temperature) on cardiac pacemaker function and conduction were studied. Our results show that these two groups of mutations have different effects on pacemaker function and conduction. Furthermore, we found that the negative effects of these mutations could be altered by external stimuli. The bradycardic effects of mutations were magnified by an increase in acetylcholine level. Changes in acid-base concentration and tissue temperature increased the ability of the SAN to recover its pacemaker function. The results of this study increase our understanding of sodium channel disorders, and help to advance research on the treatment of these conditions.
基金supported by the National Natural Science Foundation of China (21033005,21003160)the Natural Science Foundation of Shandong Province of China (ZR2010BQ003 and JQ201105)the Innovation Research Program of China University of Petroleum (27R1104067A)
文摘Hydrogels resulting from the self-assembly of small peptides are smart nanobiomaterials as their nanostructuring can be readily tuned by environmental stimuli such as pH,ionic strength and temperature,thereby favoring their practical applications.This work reports experimental observations of formation of peptide hydrogels in response to the redox environment.Ac-I 3 K-NH 2 is a short peptide amphiphile that readily self-assembles into long nanofibers and its gel formation occurs at concentrations of about 10 mmol/L.Introduction of a Cys residue into the hydrophilic region leads to a new molecule,Ac-I 3 CGK-NH 2,that enables the formation of disulfide bonds between self-assembled nanofibers,thus favoring cross-linking and promoting hydrogel formation.Under oxidative environment,Ac-I 3 CGK-NH 2 formed hydrogels at much lower concentrations(even at 0.5 mmol/L).Furthermore,the strength of the hydrogels could be easily tuned by switching between oxidative and reductive conditions and time.However,AFM,TEM,and CD measurements revealed little morphological and structural changes at molecular and nano dimensions,showing no apparent influence arising from the disulfide bond formation.
基金supported by the National Basic Research Program (973) of China (No.2007CB512100)the National High-Tech R & D Program (863) of China (No.2006AA02Z307)the National Natural Science Foundation of China (No.30570484)
文摘The aim of this study is to build two mathematical models of canine ionic currents specific to right atria and left atria.The canine left atria mathematical model was firstly modified from the Ramirez-Nattel-Courtemanche(RNC) model using the recently available experimental data of ionic currents and was further developed based on our own experimental data.A model of right atria was then built by considering the differences between right atria and left atria.The two developed models well reproduced the experimental data on action potential morphology,the rate dependence,and action potential duration restitution.They are useful for investigating the mechanisms underlying the het-erogeneity of canine regional action potentials and would help the simulation of whole heart excitation propagation and cardiac arrhythmia in the near future.
