The lack of an experimental <i>in situ</i>technique for detecting phase order in cell membranes has limited accurate studies of important processes in living organisms, such as activation of mechanosensitive pores, cell shape changes or formation of lipid domains. Dithienothiophene-based planarizable push-pull probes have been recently introduced as innovative mechanosensors that can detect and respond to the lateral forces experienced within biological membranes. The planarization in liquid- or solid-ordered lipid bilayers results in a large red shift in excitation spectra and an increased fluorescence. Several spectroscopic and imaging techniques have proven the applicability of these probes in vesicles and cells. However, the microscopic interactions involved in mechanosensing cannot be directly studied by these experiments. In this work, we elucidate the operative mechanism performing extensive all-atoms molecular dynamics simulations for hundreds of nanoseconds. Model membranes in the same conditions as in experiments were used, namely pure DOPC or DPPC bilayers, which give access to disordered and ordered phases, respectively. The probe was subjected to highly accurate parameterization using quantum mechanical calculations. The molecular dynamics simulations were rigorously compared to the experimental outcomes in order to validate the computational approach and the simulated absorption spectra resulted in agreement with previously published data. The study unveils the atomistic details of the probe planarization upon ordering of the bilayers and provides critical features of the mechanosensitivity, such as the difference in twisting angle distributions for unary, binary and ternary membrane mixtures. The acquired knowledge will promote further developments of more efficient and selective probes, e.g., targeting diversified membranes in the cell.<br/>

Twisting of a mechanosensitive molecular probe detects lipid order in membranes

2019 Spring National Meeting

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