3 research outputs found
Nanoactuator for Neuronal Optoporation
Light-driven modulation of neuronal activity at high
spatial-temporal
resolution is becoming of high interest in neuroscience. In addition
to optogenetics, nongenetic membrane-targeted nanomachines that alter
the electrical state of the neuronal membranes are in demand. Here,
we engineered and characterized a photoswitchable conjugated compound
(BV-1) that spontaneously partitions into the neuronal membrane and
undergoes a charge transfer upon light stimulation. The activity of
primary neurons is not affected in the dark, whereas millisecond light
pulses of cyan light induce a progressive decrease in membrane resistance
and an increase in inward current matched to a progressive depolarization
and action potential firing. We found that illumination of BV-1 induces
oxidation of membrane phospholipids, which is necessary for the electrophysiological
effects and is associated with decreased membrane tension and increased
membrane fluidity. Time-resolved atomic force microscopy and molecular
dynamics simulations performed on planar lipid bilayers revealed that
the underlying mechanism is a light-driven formation of pore-like
structures across the plasma membrane. Such a phenomenon decreases
membrane resistance and increases permeability to monovalent cations,
namely, Na+, mimicking the effects of antifungal polyenes.
The same effect on membrane resistance was also observed in nonexcitable
cells. When sustained light stimulations are applied, neuronal swelling
and death occur. The light-controlled pore-forming properties of BV-1
allow performing āon-demandā light-induced membrane
poration to rapidly shift from cell-attached to perforated whole-cell
patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex
elicited neuronal firing in response to short trains of light stimuli,
followed by activity silencing upon prolonged light stimulations.
BV-1 represents a versatile molecular nanomachine whose properties
can be exploited to induce either photostimulation or space-specific
cell death, depending on the pattern and duration of light stimulation
Nanoactuator for Neuronal Optoporation
Light-driven modulation of neuronal activity at high
spatial-temporal
resolution is becoming of high interest in neuroscience. In addition
to optogenetics, nongenetic membrane-targeted nanomachines that alter
the electrical state of the neuronal membranes are in demand. Here,
we engineered and characterized a photoswitchable conjugated compound
(BV-1) that spontaneously partitions into the neuronal membrane and
undergoes a charge transfer upon light stimulation. The activity of
primary neurons is not affected in the dark, whereas millisecond light
pulses of cyan light induce a progressive decrease in membrane resistance
and an increase in inward current matched to a progressive depolarization
and action potential firing. We found that illumination of BV-1 induces
oxidation of membrane phospholipids, which is necessary for the electrophysiological
effects and is associated with decreased membrane tension and increased
membrane fluidity. Time-resolved atomic force microscopy and molecular
dynamics simulations performed on planar lipid bilayers revealed that
the underlying mechanism is a light-driven formation of pore-like
structures across the plasma membrane. Such a phenomenon decreases
membrane resistance and increases permeability to monovalent cations,
namely, Na+, mimicking the effects of antifungal polyenes.
The same effect on membrane resistance was also observed in nonexcitable
cells. When sustained light stimulations are applied, neuronal swelling
and death occur. The light-controlled pore-forming properties of BV-1
allow performing āon-demandā light-induced membrane
poration to rapidly shift from cell-attached to perforated whole-cell
patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex
elicited neuronal firing in response to short trains of light stimuli,
followed by activity silencing upon prolonged light stimulations.
BV-1 represents a versatile molecular nanomachine whose properties
can be exploited to induce either photostimulation or space-specific
cell death, depending on the pattern and duration of light stimulation
Nanoactuator for Neuronal Optoporation
Light-driven modulation of neuronal activity at high
spatial-temporal
resolution is becoming of high interest in neuroscience. In addition
to optogenetics, nongenetic membrane-targeted nanomachines that alter
the electrical state of the neuronal membranes are in demand. Here,
we engineered and characterized a photoswitchable conjugated compound
(BV-1) that spontaneously partitions into the neuronal membrane and
undergoes a charge transfer upon light stimulation. The activity of
primary neurons is not affected in the dark, whereas millisecond light
pulses of cyan light induce a progressive decrease in membrane resistance
and an increase in inward current matched to a progressive depolarization
and action potential firing. We found that illumination of BV-1 induces
oxidation of membrane phospholipids, which is necessary for the electrophysiological
effects and is associated with decreased membrane tension and increased
membrane fluidity. Time-resolved atomic force microscopy and molecular
dynamics simulations performed on planar lipid bilayers revealed that
the underlying mechanism is a light-driven formation of pore-like
structures across the plasma membrane. Such a phenomenon decreases
membrane resistance and increases permeability to monovalent cations,
namely, Na+, mimicking the effects of antifungal polyenes.
The same effect on membrane resistance was also observed in nonexcitable
cells. When sustained light stimulations are applied, neuronal swelling
and death occur. The light-controlled pore-forming properties of BV-1
allow performing āon-demandā light-induced membrane
poration to rapidly shift from cell-attached to perforated whole-cell
patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex
elicited neuronal firing in response to short trains of light stimuli,
followed by activity silencing upon prolonged light stimulations.
BV-1 represents a versatile molecular nanomachine whose properties
can be exploited to induce either photostimulation or space-specific
cell death, depending on the pattern and duration of light stimulation