Photoswitchable microtubule stabilisers optically control tubulin cytoskeleton structure and function

Abstract

Small molecule inhibitors provide a versatile method for studies in microtubule cytoskeleton research, since tubulin is not readily amenable to functional control using genetics. However, traditional chemical inhibitors do not allow spatiotemporally precise applications on the length and time scales appropriate for selectively modulating microtubule-dependent processes. We have synthesised a panel of taxane-based light-responsive microtubule stabilisers, whose tubulin hyperpolymerisation activity can be induced by photoisomerisation to their thermodynamically metastable state. These reagents can be isomerised in live cells, optically controlling microtubule network integrity, cell cycle repartition, and cell survival, and offering biological response on the timescale of seconds and spatial precision to the level of individual cells. These azobenzene-based microtubule stabilisers offer the possibility of noninvasive, highly spatiotemporally precise modulation of the microtubule cytoskeleton in live cells, and can prove powerful reagents for studies of intracellular transport, cell motility, and neurodegeneration.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/778993v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (82K):\norg.highwire.dtl.DTLVardef@22a5forg.highwire.dtl.DTLVardef@2c018dorg.highwire.dtl.DTLVardef@119e288org.highwire.dtl.DTLVardef@677229_HPS_FORMAT_FIGEXP M_FIG C_FIG