Mechanical systems biology of C. elegans touch sensation

Abstract

The sense of touch informs us of the physical properties of our surroundings and is a critical aspect of communication. Before touches are perceived, mechanical signals are transmitted quickly and reliably from the skin’s surface to mechano-electrical transduction channels embedded within specialized sensory neurons. We are just beginning to understand how soft tissues participate in force transmission and how they are deformed. Here, we review empirical and theoretical studies of single molecules and molecular ensembles thought to be involved in mechanotransmission and apply the concepts emerging from this work to the sense of touch. We focus on the nematode Caenorhabditis elegans as a well-studied model for touch sensation in which mechanics can be studied on the molecular, cellular, and systems level. Finally, we conclude that force transmission is an emergent property of macromolecular cellular structures that mutually stabilize one another.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans

“…The touch neurons PLM and ALM are microtubule-rich and use specific microtubules to transmit mechanical stimuli (72). Treatment with colchicine, a drug that can cause microtubule depolymerization or damage to microtubule cytoskeleton, reduced overall gene expression in touch neurons (73).…”

Pneumatic stimulation of C. elegans mechanoreceptor neurons in a microfluidic trap

“…The roundworm Caenorhabditis elegans is an excellent system to study mechanical stress transmission during touch, since its mechanoreceptors are well characterized on the molecular, 9,10 physiological, 11–13 and mechanical 5,14 levels. Genetic, molecular, and physiological tools to visualize forces on single molecules in live animals 14,15 are readily accessible.…”

“…Genetic, molecular, and physiological tools to visualize forces on single molecules in live animals 14,15 are readily accessible. The transparent body of C. elegans facilitates high-resolution imaging down to the level of individual protein complexes.…”

“…5 The anatomy and molecular composition of C. elegans cuticle and its underlying epidermis (referred to as ‘skin’ hereafter) is very well characterized, 16 enabling manipulation and investigation of the skin’s mechanics and its role in mechanosensation. 14 …”

Acetylated tubulin is essential for touch sensation in mice

“…For example, the bacterial mechanotransduction channel MscS (Sukharev, 2002) and eukaryotic two-pore-domain potassium channels TRAAK and TREK1 (Brohawn et al, 2014a, 2012, 2014b; Lolicato et al, 2014) are fully activated by mechanical stimuli when reconstituted in reduced membrane systems, and the mechanosensitive ion channel Piezo1 is also likely to be gated by force exerted via lipids due to its exceptional sensitivity to membrane tension (Cox et al, 2016; Lewis and Grandl, 2015). However, in-vivo, membrane ion channels are not isolated from the cytoplasm and extracellular matrix, and mechanical sensitivity may depend on further interaction with other cellular components such as the underlying cytoskeleton to modify and redistribute membrane tension (Delmas et al, 2011; Krieg et al, 2015; Qi et al, 2015). Indeed, in Drosophila , NompC ion channels were shown to be linked between the plasma membrane and microtubules by a tether protein domain in the N-terminus of the channel, and this linkage is essential for mechanosensitivity of the channel (Zhang et al, 2015).…”