A fluorescent membrane tension probe

Colom, Adai; Derivery, Emmanuel; Soleimanpour, Saeideh; Tomba, Caterina; Molin, Marta Dal; Sakai, Naomi; González‐Gaitán, Marcos; Matile, Stefan; Roux, Aurélien

doi:10.1038/s41557-018-0127-3

Cited by 425 publications

(570 citation statements)

References 58 publications

Supporting

Mentioning

538

Contrasting

Unclassified

Order By: Relevance

“…The latter is attractive for concentration‐independent force imaging by FLIM (fluorescence lifetime imaging microscopy) . According to FLIM images of 1 in homogeneous lipid bilayer membranes, the application of tension is reported as linearly decreasing lifetimes, with slopes depending on the lipid composition . This trend is consistent with flipper deplanarization upon lipid decompression (Figure b).…”

Section: Introductionsupporting

confidence: 72%

“…Namely, increasing planarization in the ground state will result in increasingly planar FC excited states and thus decreasing losses from relaxation into fully twisted, non‐emissive TICT‐like excited states of 2 . This record mechanosensitivity with regard not only to redshifted excitation but also to fluorescence intensity and lifetime, suggested that CF 3 flipper 2 could, in principle, outperform CH 3 original 1 as fluorescent membrane tension probe in living cells.…”

Section: Resultsmentioning

confidence: 95%

“…[4,5] According to FLIM images of 1 in homogeneous lipid bilayer membranes, the applicationo ft ension is reporteda s linearly decreasing lifetimes, with slopesd epending on the lipid composition. [6] This trend is consistentw ith flipperd eplanarization upon lipid decompression (Figure 1b). In heterogeneous lipid bilayer membranes,the application of tension is reported as linearly increasing lifetimes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fluorescent Flipper Probes: Comprehensive Twist Coverage

Straková

Poblador‐Bahamonde

Sakai

et al. 2019

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

To image the membrane tension in living cells, planarizable push–pull probes have been introduced. The first operational probe is built around two dithieno[3,2‐b:2′,3′‐d]thiophenes (DTTs) that are twisted out of co‐planarity and polarized with donors and acceptors at either end. In this report, the chemical space available for the twisting of “flipper probes” is assessed comprehensively. The result is, not surprisingly, that every atom matters: Removal of one methyl group in the twist region yields probes that planarize already in solution and are thus less sensitive to membrane tension. Addition of one or more carbons in the same region hinders non‐interfering probe alignment along lipid tails and thus partitioning into lipid bilayer membranes as well as mechanosensitivity. However, substitution of one methyl by an isosteric trifluoromethyl group in the twist region, achieved by quite substantial multistep organic synthesis, yields excitation maxima that shift over +100 nm to the red in response to increasing order of the surrounding membrane. This record redshift comes with record changes in fluorescence intensity and lifetime, high push–pull transition dipoles and higher rotational barriers. Supported by distinct dependence on viscosity and twist of the push–pull probes, kinetic competition between dark, fully twisted and bright, fully planarized relaxed excited states emerges as unifying origin of fluorescence quantum yields.

show abstract

Section: Introductionsupporting

confidence: 72%

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fluorescent Flipper Probes: Comprehensive Twist Coverage

Straková

Poblador‐Bahamonde

Sakai

et al. 2019

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several other derivatives with different headgroups failed to do so (not shown). [5] In summary,these results identify all new members of the double-mutant cycle 1-4 as operational membrane tension probes,w ith general access to chemical stability being the most significant advance,f ollowed by red shifts that add up perfectly to reach important values.T hey introduce doublemutant cycle analysis to fluorescent membrane probes and, most importantly,v alidate an ew,g eneral and fundamental concept that functions with non-trivial supramolecular chemistry,s olves practical problems,a se xemplified with the flipper dilemma, and opens broad new perspectives. This decrease was as for original 1,t hus correctly reporting decreasing membrane tension as tension-induced disassembly of more ordered microdomains.…”

Section: In Memory Of Koji Nakanishimentioning

confidence: 71%

“…

…”

mentioning

confidence: 99%

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

et al. 2019

Self Cite

View full text Add to dashboard Cite

Planarizable push-pull probes have been introduced to demonstrate physical forces in biology.However,the donors and acceptors needed to polarizem echanically planarized probes are incompatible with their twisted resting state.T he objective of this study was to overcome this "flipper dilemma" with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe.T his concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability,red shifts adding up to high significance,and focused mechanosensitivity.M ost important, however,i st he introduction of an ew,g eneral and fundamental concept that operates with non-trivial supramolecular chemistry,solves an important practical problem and opens aw ide chemical space.Planarizable push-pull (PP) chromophores have been introduced [1] as mechanosensitive [2] fluorescent membrane probes [1][2][3] to image membrane tension [4] in living cells. [5,6] The current best is constructed around twisted dithienothiophene (DTT) dithienothiophene S,S-dioxide (DTTO2) conjugates ( Figure 1a,D ' = S, A' = SO 2 ). [7] Thet wo "flippers" [7] are twisted out of coplanarity by repulsion between the methyls (light blue circles) and the s holes (dark blue ovals) [8][9][10][11] on the sulfurs next to the connecting bond (Figure 1b,l eft, 1). The PP system is prepared first with "sulfide" donors and "sulfone" acceptors in the DTT and the DTTO2b ridges, respectively (Figure 1b, 8,9). Conjugation of DTT and DTTO2u pon mechanical co-planarization then turns on this intrinsic PP system and shifts the excitation maximum to the red (Figure 1b,r ight). Thee mission maximum is nearly mechanoinsensitive because the probes emit only from the planar form. [12] To achieve significant red shifts upon planarization in the ground state,a dditional PP donors Da nd acceptors Aa re required (Figure 1a). These exocyclics ubstituents represent atrue dilemma because in the twisted resting state,the DTT donors and DTTO2 acceptors,a tl east partially decoupled from each other and equipped with extra Da nd A, could become too rich and too poor in electron density,respectively, and decompose easily (Figure 1a). Because both DTTs and DTTO2are comparably electron-rich, [13] this problem is more pronounced on the DTT side.T herefore,Dand As hould ideally turn on only in response to flipper planarization. Sulfides,p reviously introduced as covalent PP turn-on donors, [12] failed to afford operational probes. [14] Non-covalent 1,4-chalcogen bonds (1,4-CBs) [8][9][10][11] as in 1 were more successful, also because spontaneous degradation into reactive Figure 1. a) Flipper dilemma and b) CB cascade switch:a)Inplanarizable PP probes, exocyclic donors D D and acceptors A A are needed in planar but incompatiblew ith twisted form. b) Twisting of the central bond (1)turns off PP D D (2,r ed circle), and A A (3,b lue circle) because Lewis base Y( 5)hardly ...

show abstract

Engineering Lipid Membranes with Programmable DNA Nanostructures

et al. 2019

View full text Add to dashboard Cite

Lipid and DNA are abundant biomolecules with critical functions in cells. The water-insoluble, amphipathic lipid molecules are best known for their roles in energy storage (e.g. as triglyceride), signaling (e.g. as sphingolipid), and compartmentalization (e.g. by forming membrane-enclosed bodies). The soluble, highly negatively charged DNA, which stores cells' genetic information, has proven to be an excellent material for constructing programmable nanostructures in vitro thanks to its self-assembling capabilities. These two seemingly distant molecules make contact within cell nuclei, often via lipidated proteins, with proposed functions of modulating chromatin structures. Carefully formulated lipid/DNA complexes are promising reagents for gene therapy. The past few years saw an emerging research field of interfacing DNA nanostructures with lipid membranes, with an overarching goal of generating DNA/lipid hybrid materials that possess novel and controllable structure, dynamics, and function. An arsenal of DNA-based tools has been created to coat, mold, deform, and penetrate lipid bilayers, affording us the ability to manipulate membranes with nanoscopic precision. These membrane engineering methods not only enable quantitative biophysical studies, but also open new opportunities in synthetic biology (e.g. artificial cells) and therapeutics (e.g. drug delivery).

show abstract

A fluorescent membrane tension probe

Cited by 425 publications

References 58 publications

Fluorescent Flipper Probes: Comprehensive Twist Coverage

Fluorescent Flipper Probes: Comprehensive Twist Coverage

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

Engineering Lipid Membranes with Programmable DNA Nanostructures

Contact Info

Product

Resources

About