Mechanotransduction is the fundamental biophysical process that underlies the senses of touch, balance, proprioception, and hearing, and is mediated by mechanosensitive protein complexes that effectively couple the action of external mechanical forces to the opening of specialized ion channels. In general, how these molecular complexes work remains a mystery, even though the proteins involved have been identified and many of their structures solved. This knowledge gap is largely because of the difficulties in obtaining working quantities of mechanosensory complexes to allow proper biophysical and biochemical characterization at the molecular level. The six touch receptor neurons found in the pioneer nematode C. elegans are an ideal system to study the function of mechanotransduction complexes that enable nematodes to feel and react to gentle touch. Furthermore, we can evaluate critical malfunctions in these complexes that lead to pathological conditions such as neurodegeneration. My research interest consists in studying the molecular mechanism underlying the activity of these mechanotransduction complexes that allow the nematode to perceive and respond to mechanical stimuli. We apply combined tools of genetics, biochemistry, live imaging, electrophysiology and force spectroscopy to dissect the molecular mechanisms of touch sensation from single molecules to whole animal levels. What are the roles of each protein within the complex? What is their structural arrangement? Are there intracellular and extracellular elements acting on the gating mechanism? What are the minimal components required for assembling functional complexes? Can we rescue defective or damaged complexes? These are some of the questions we aim to tackle. This research is fundamental to help understand the operation of more complex mechanotransduction systems such as the ones found in the skin and inner ear of mammals, which presumably are subject to similar molecular forces and energy landscapes, and therefore may share significant aspects in their gating mechanisms.

• Interspecies relationships of natural amoebae and bacteria with C. elegans create environments propitious for multigenerational diapause. Marcela Serey, Esteban Retamales, Gabriel Ibañez, Gonzalo Riadi, Patricio Orio, Juan P. Castillo**, and Andrea Calixto**. mSystems. 2025. 0:e01566-24. https://doi.org/10.1128/msystems.01566-24
• Assignment of Structural Transitions During the Mechanical Unwrapping of Nucleosomes and their Disassembly Products. César Díaz-Celis*, Cristhian Cañari-Chumpitaz*, Robert P. Sosa*, Juan P. Castillo*, Meng Zhang, Enze Cheng, Andy Chen, Michael Vien, JeongHoon Kim, Bibiana Onoa, and Carlos Bustamante. PNAS. 2022. 119(33), e2206513119. https://doi.org/10.1073/pnas.2206513119
• A DNA packaging motor inchworms along one strand allowing it to adapt to alternative double-helical structures. Juan P. Castillo*, Alexander Tong*, Sara Tafoya, Paul J. Jardine & Carlos Bustamante. Nat. Commun. 2021. 12:3439. https://doi.org/10.1038/s41467-021-23725-5
• β1-subunit-induced structural rearrangements of the Ca2+- and voltage-activated K+ (BK) channel. Castillo JP*, Sánchez-Rodríguez JE*, Hyde HC*, Zaelzer CA, Aguayo D, Sepúlveda RV, Luk LY, Kent SB, Gonzalez-Nilo FD, Bezanilla F, Latorre R. PNAS. 2016. 113(23):E3231-9. https://doi.org/10.1073/pnas.1606381113
• Mechanism of potassium ion uptake by the Na+/K+-ATPase. Juan P. Castillo, Huan Rui, Daniel Basilio, Avisek Das, Benoit Roux, Ramon Latorre, Francisco Bezanilla, and Miguel Holmgren. Nat. Commun. 2015. 6:7622. https://doi.org/10.1038/ncomms8622
• Temperature and voltage coupling to channel opening in transient receptor potential melastatin 8 (TRPM8). Raddatz N*, Castillo JP*, Gonzalez C, Alvarez O, Latorre R. J Biol Chem. 2014. 289(51): 35438-54. https://doi.org/10.1074/jbc.M114.612713