A Rationally Designed, General Strategy for Membrane Orientation of Photoinduced Electron Transfer-Based Voltage-Sensitive Dyes

Kulkarni, Rishikesh U.; Yin, Hang; Pourmandi, Narges; James, Feroz; Adil, Maroof M.; Schaffer, David V.; Wang, Yi; Miller, Evan W.

doi:10.1021/acschembio.6b00981

Cited by 52 publications

(88 citation statements)

References 40 publications

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“…Rapid synaptic integration may be facilitated by higher maturity of transplanted cells. Using voltage‐sensitive fluorescent dyes to monitor spiking activity—a hallmark of neuronal maturation—we observed that 80% of 3D‐generated neurons fired action potentials at D31 of differentiation in vitro (Figure S13, Supporting Information). Such functionally mature neurons may integrate with the host neuronal architecture faster, and lead to rapid alleviation of disease symptoms.…”

Section: Resultsmentioning

confidence: 99%

“…Voltage‐Sensitive Dye‐Based Imaging : D31 H1 hESC‐derived mDA neurons generated in pNIPAAm‐PEG hydrogels and seeded on laminin‐coated coverslips were labeled with voltage‐sensitive dyes dsVF2.2(OMe).Cl (500 × 10 −9 m ), and images were acquired with a W‐Plan‐Apo 63×/1.0 objective (Zeiss) and OrcaFlash4.0 sCMOS camera (sCMOS, Hamamatsu) and analyzed as previously described …”

Section: Methodsmentioning

confidence: 99%

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Dopaminergic Neurons Transplanted Using Cell‐Instructive Biomaterials Alleviate Parkinsonism in Rodents

Adil

Rao

Ramadoss

et al. 2018

Adv Funct Materials

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Cell replacement therapy (CRT) is a promising treatment for degenerative disorders, such as Parkinson's disease (PD). However, CRT is in general hindered by poor graft survival, limited cell dispersion, modest cell integration, and delayed therapeutic efficacy. These challenges need to be addressed to enhance the clinical translation of CRT. Here, key bioactive factors that increase the survival and dispersion of human pluripotent stem cell-derived midbrain dopaminergic (mDA) neurons, the primary type of cells lost in PD, are identified. mDA neurons cotransplanted with survival and dispersion factors within a protective hyaluronic acid hydrogel, optimized for controlled factor release and cell spread, alleviate disease symptoms in PD model rats. Importantly, treatment benefits correlate with increased graft survival, dispersion, and integration. Optimally engineered cell-instructive transplantation platforms thus offer promise for enhancing CRT in PD and potentially a range of degenerative diseases or trauma.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dopaminergic Neurons Transplanted Using Cell‐Instructive Biomaterials Alleviate Parkinsonism in Rodents

Adil

Rao

Ramadoss

et al. 2018

Adv Funct Materials

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“…VoltageFluor dyes do both of these well, and bath application of VF dyes gives membrane localized fluorescence. 12, 14 However, small molecule voltage indicators display poor selectivity for particular cell types and stain all membranes, making cellular resolution difficult. 13, 16 We have developed photoactivation methods to address the problem of contrast, 17 and development of complementary approaches with genetically encoded components is underway in our lab.…”

Section: Universal Challenges For Voltage Imagingmentioning

confidence: 99%

Voltage Imaging: Pitfalls and Potential

Kulkarni

Miller

2017

Biochemistry

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Optical methods to interrogate membrane potential changes in neurons promise to revolutionize our ability to dissect the activity of individual cells embedded in neural circuits underlying behavior and sensation. A number of voltage imaging strategies have emerged in the last few years. This Perspective discusses developments in both small molecule and genetically-encoded fluorescent indicators of membrane potential. We survey recent advances in small molecule fluorescent indicators that rely on photoinduced electron transfer (PeT) to sense voltage as well as refinements of voltage-sensitive fluorescent proteins and new opsin-based strategies for monitoring voltage changes. We compare the requirements of fluorescent voltage indicators to those for more canonical Ca2+ sensing as a way to illuminate the particular challenges associated with voltage imaging.

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“…5,[34][35][36] Therefore, we were eager to adapt phosphorous-substituted xanthenes into a fluorescent sensing scaffold. Previous work in our lab suggests that xanthene dyes with a range of bridgehead (O, 37 C, 27 Si 38 ) and terminal atoms (O 27, 37 or substituted N [38][39] can be employed as voltage-sensitive dyes via introduction of a lipophilic, conjugated molecular wire. We hypothesized that the installation of phenylenevinylene molecular wires into the context of a phosphorous-subsituted xanthene dye would yield voltage-sensitive indicators with emission and excitation maxima above 700 nm.…”

mentioning

confidence: 99%

Voltage Imaging with a NIR-Absorbing Phosphine Oxide Rhodamine Voltage Reporter

González¹,

Walker²,

Cao³

et al. 2019

Preprint

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Near infrared (NIR) fluorophores may hold the key for non-invasive optical imaging of deep structures in intact organisms with high spatial and temporal resolution. Yet, developing fluorescent dyes that emit and absorb light at wavelengths greater than 700 nm and that respond to biochemical and biophysical events in living systems remains an outstanding challenge. Here, we report the design, synthesis, and application of NIR-absorbing and -emitting, sulfonated, phosphine-oxide (po) rhodamines for voltage imaging in thick tissue from the central nervous system. We find po-rhodamine based voltage reporters, or poRhoVRs, display NIR excitation and emission profiles at greater than 700 nm, show best-in class voltage sensitivity (up to 43% ΔF/F per 100 mV in HEK cells), and can be combined with existing optical sensors, like Ca 2+ -sensitive fluorescent proteins (GCaMP), and actuators, like light-activated opsins ChannelRhodopsin-2 (ChR2). Simultaneous voltage and Ca 2+ imaging reveals differences in activity dynamics in rat hippocampal neurons, and pairing poRhoVR with blue-light based ChR2 affords all-optical electrophysiology. In ex vivo retinas isolated from a mouse model of retinal degeneration, poRhoVR, together with GCaMP-based Ca 2+ imaging and traditional multi-electrode array (MEA) recording, can provide a comprehensive physiological activity profile of neuronal activity. Taken together, these experiments establish that poRhoVR will open new horizons in optical interrogation of cellular and neuronal physiology in intact systems.

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A Rationally Designed, General Strategy for Membrane Orientation of Photoinduced Electron Transfer-Based Voltage-Sensitive Dyes

Cited by 52 publications

References 40 publications

Dopaminergic Neurons Transplanted Using Cell‐Instructive Biomaterials Alleviate Parkinsonism in Rodents

Dopaminergic Neurons Transplanted Using Cell‐Instructive Biomaterials Alleviate Parkinsonism in Rodents

Voltage Imaging: Pitfalls and Potential

Voltage Imaging with a NIR-Absorbing Phosphine Oxide Rhodamine Voltage Reporter

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