Message in a Living Cell

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Dr. Leif Dehmelt >

Phone: +49 (231) 755 7057



Dr. Yaowen Wu

Phone: +49 (231) 133-2943



Original Publication

Chen X, Venkatachalapathy M, Kamps D, Weigel S, Kumar R, Orlich M, Garrecht R, Hirtz M, Niemeyer CM, Wu YW, Dehmelt L. (2017). "Molecular-Activity Painting": Switch-like, Light-Controlled Perturbations inside Living Cells. Angew Chem Int Ed Engl
doi: 10.1002/anie.201611432.

Cells communicate with their environment through their plasma membrane (PM). It serves as a signaling hub to control crucial cellular processes. Observation and investigation of these processes is problematic due to the high fluidity of the plasma membrane. The group of Leif Dehmelt and Yaowen Wu developed a “Molecular Activity Painting” technique that allows the study of signal transduction processes at the PM.

April 12, 2017

The plasma membrane primarily serves to separate and protect the cell from the outside environment. It is also the direct connection to the environment, senses and filters a variety of stimuli. Extracellular signals are transduced by protein receptors through the membrane, that can freely diffuse and thereby locally respond and trigger processes like cell movement. However, the plasma membrane is also a very fluid structure, which complicates the study of such processes.

The teams of Leif Dehmelt and Yaowen Wu in collaboration with the Wu Group from the Chemical Genomic Centre developed a new strategy termed "Molecular Activity Painting" (MAP) to interfere and observe signal transduction at the PM, published in the journal “Angewandte Chemie”. This strategy combines immobilization and light-controlled activation: Artificial receptors tightly anchored on the cell substrate are furnished with a designed modular molecular system. One light pulse activates the modular building blocks, which can trigger localized signal cascades.

The core of the MAP technology is a soluble multicomponent molecule assembled from four functional parts: a chloroalkyl moiety, a polymeric (PEG) linker, a molecular group called trimethroprim or TMP, and a light-sensitive group called Nvoc. This "caged chemical dimerizer", as it is called, can fulfill several tasks: Via its chloroalkyl moiety, it binds to an artificial receptor, which is tightly anchored and immobilized on the cell substrate. The Nvoc group can be removed ("uncaged") by a single light pulse. The uncaged TMP moiety is then targeted by a designed factor to induce a signal cascade in the cell. The whole system is aimed at one purpose: control and visualization of molecular function in living cells.

To validate this technique, the scientists used the small GTPase RhoA, which is known to stimulate the formation of contractile actin structures, as a “molecular paint”. By “painting” the letter “N” on the PM of a living cell the scientists were able to induce a patterned actomyosin contraction. “The beauty of this method is its universal applicability. Molecular Activity Painting allows to selectively control the localisation of regulatory signal transduction processes in living cells on a micrometre-scale” the authors explains.

JJ/PH



The text is based on "What Happens in the Living Cell?"

 
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