Taming twisted light with topology
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Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels
The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate neurons to millimeter depth with sub-cellular specificity and millisecond temporal resolution, it can also cause heating of the targeted tissue. On the other hand, sonogenetics can non-invasively modulate the cellular activity of neurons expressed with mechano-sensitive proteins in deeper areas of the brain with less spatial selectivity. We present a theoretical analysis of a synergistic sono-optogenetic method to overcome these limitations by co-expressing a mechano-sensitive (MscL-I92L) ion-channel with a light-sensitive (CoChR/ChroME2s/ChRmine) ion-channel in hippocampal neurons. It is shown that in the presence of low-amplitude subthreshold ultrasound pulses, the two-photon excitation threshold for neural spiking reduces drastically by 73% with MscL-I92L-CoChR (0.021 mW/µm2), 66% with MscL-I92L-ChroME2s (0.029 mW/µm2), and 64% with MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. It allows deeper excitation of up to 1.2 cm with MscL-I92L-ChRmine combination. The method is useful to design new experiments for low-power deep excitation of neurons and multimodal neuroprosthetic devices and circuits.
Archaean green-light environments drove the evolution of cyanobacteria’s light-harvesting system
Cyanobacteria induced the great oxidation event around 2.4 billion years ago, probably triggering the rise in aerobic biodiversity. While chlorophylls are universal pigments used by all phototrophic organisms, cyanobacteria use additional pigments called phycobilins for their light-harvesting antennas—phycobilisomes—to absorb light energy at complementary wavelengths to chlorophylls. Nonetheless, an enigma persists: why did cyanobacteria need phycobilisomes? Here, we demonstrate through numerical simulations that the underwater light spectrum during the Archaean era was probably predominantly green owing to oxidized Fe(III) precipitation. The green-light environments, probably shaped by photosynthetic organisms, may have directed their own photosynthetic evolution. Genetic engineering of extant cyanobacteria, simulating past natural selection, suggests that cyanobacteria that acquired a green-specialized phycobilin called phycoerythrobilin could have flourished under green-light environments. Phylogenetic analyses indicate that the common ancestor of modern cyanobacteria embraced all key components of phycobilisomes to establish an intricate energy transfer mechanism towards chlorophylls using green light and thus gained strong selective advantage under green-light conditions. Our findings highlight the co-evolutionary relationship between oxygenic phototrophs and light environments that defined the aquatic landscape of the Archaean Earth and envision the green colour as a sign of the distinct evolutionary stage of inhabited planets.
Diurnal cycles drive rhythmic physiology and promote survival in facultative phototrophic bacteria
Bacteria have evolved many strategies to spare energy when nutrients become scarce. One widespread such strategy is facultative phototrophy, which helps heterotrophs supplement their energy supply using light. Our knowledge of the impact that such behaviors have on bacterial fitness and physiology is, however, still limited. Here, we study how a representative of the genus Porphyrobacter, in which aerobic anoxygenic phototrophy is ancestral, responds to different light regimes under nutrient limitation. We show that bacterial survival in stationary phase relies on functional reaction centers and varies depending on the light regime. Under dark-light alternance, our bacterial model presents a diphasic life history dependent on phototrophy: during dark phases, the cells inhibit DNA replication and part of the population lyses and releases nutrients, while subsequent light phases allow for the recovery and renewed growth of the surviving cells. We correlate these cyclic variations with a pervasive pattern of rhythmic transcription which reflects global changes in diurnal metabolic activity. Finally, we demonstrate that, compared to either a phototrophy mutant or a bacteriochlorophyll a overproducer, the wild type strain is better adapted to natural environments, where regular dark-light cycles are interspersed with additional accidental dark episodes. Overall, our results highlight the importance of light-induced biological rhythms in a new model of aerobic anoxygenic phototroph representative of an ecologically important group of environmental bacteria.
The apoplastic pH is a key determinant in the hypocotyl growth response to auxin dosage and light
Auxin is a core phytohormone regulating plant elongation growth. While auxin typically promotes hypocotyl elongation, excessive amounts of auxin inhibit elongation. Moreover, auxin usually promotes light-grown, but inhibits dark-grown hypocotyl elongation. How dosage and light condition change the plant’s response to auxin, also known as auxin’s biphasic effect or dual effect, has long been mysterious. Auxin induces cell expansion primarily through apoplastic acidification and the subsequent ‘acid growth’ mechanism. Here we show that this pathway operates for both stimulatory and inhibitory auxin doses and under both dark and light conditions. Regardless of the dosage, more auxin induces more transcripts of SAURs (Small Auxin-Up RNAs), leading to a stronger activation of plasma membrane H+-ATPases (AHAs) and progressive acidification of the apoplast in hypocotyl epidermis. Apoplastic acidification promotes growth but only above a certain pH threshold, below which excessive acidification inhibits elongation. Auxin overdosage-triggered hypocotyl inhibition can be alleviated by suppressing the AHA activity or raising the apoplastic pH. Light-grown hypocotyls exhibit a higher apoplastic pH, which impedes cell elongation and counteracts auxin-induced over-acidification. Auxin and light antagonistically regulate the SAUR-PP2C.D-AHA pathway in the hypocotyl and influence plant elongation growth. Our findings suggest that the biphasic effect of auxin results from the biphasic response of hypocotyl cells to decreasing apoplastic pH.
Responsive DNA artificial cells for contact and behavior regulation of mammalian cells
Artificial cells have emerged as synthetic entities designed to mimic the functionalities of natural cells, but their interactive ability with mammalian cells remains challenging. Herein, we develop a generalizable and modular strategy to engineer DNA-empowered stimulable artificial cells designated to regulate mammalian cells (STARM) via synthetic contact-dependent communication. Constructed through temperature-controlled DNA self-assembly involving liquid-liquid phase separation (LLPS), STARMs feature organized all-DNA cytoplasm-mimic and membrane-mimic compartments. These compartments can integrate functional nucleic acid (FNA) modules and light-responsive gold nanorods (AuNRs) to establish a programmable sense-and-respond mechanism to specific stimuli, such as light or ions, orchestrating diverse biological functions, including tissue formation and cellular signaling. By combining two designer STARMs into a dual-channel system, we achieve orthogonally regulated cellular signaling in multicellular communities. Ultimately, the in vivo therapeutic efficacy of STARM in light-guided muscle regeneration in living animals demonstrates the promising potential of smart artificial cells in regenerative medicine.
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