About

Ronald S. Rock is an Associate Professor of Biochemistry and Molecular Biology at the University of Chicago. His research focuses on understanding biological motion, specifically how motor proteins such as myosins navigate the cytoskeleton and dynamically organize cells. His group employs a multifaceted approach that includes constructing advanced single-molecule fluorescence microscopes and optical tweezers to observe myosin movement both in vitro and within whole cells. Additionally, he utilizes structural biology tools to investigate how myosin architecture and quaternary structure regulate motility. Dr. Rock's academic background includes a B.S. in Chemistry from the University of Chicago, a Ph.D. in Chemistry from Caltech, and a postdoctoral fellowship at Stanford University in the Spudich Lab. His notable contributions involve quantifying intracellular distributions of HaloTag-labeled proteins, exploring actin imaging with optogenetic tools, and studying the behavior of myosin 10 in cellular structures such as filopodia. His work has implications for understanding cellular transport mechanisms and the regulation of the cytoskeleton, with applications in cancer metastasis and cell motility.

Research topics

• Cell biology
• Biophysics
• Biology
• Biochemistry
• Neuroscience
• Genetics
• Chemistry
• Botany

Selected publications

• Dynamic Myosin 10 coupling to DCC and β1 integrin is mediated by intrinsically disordered regions during filopodial transport and patterning

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-14

  articleOpen accessSenior authorCorresponding

  Abstract Intrinsically disordered regions (IDRs) are key mediators of protein-protein interactions. IDRs are important components of Myosin 10 (Myo10) and cargo complexes that influence neuronal development and cell growth, yet how IDRs dictate Myo10’s cargo affinity and selectivity is not fully understood. Here, we investigate how the actin motor protein Myo10 engages two distinct cargo receptors, DCC and β1 integrin, in cellular protrusions known as filopodia. Using hydrogen-deuterium exchange mass spectrometry (HDX-MS), cross-linking mass spectrometry (XL-MS), live-cell imaging, and super-resolution microscopy, we show that Myo10 decodes IDR elements through two complementary mechanisms: disorder-to-order transitions and “fuzzy” binding. The cytoplasmic portion of DCC binds Myo10 via a weakly helical P3 motif that acts as a preformed recognition element, while additional disordered motifs contribute to affinity through dynamic, weak interactions. In contrast, the β1 integrin tail interacts with Myo10 through short NPxY motifs that remain disordered. Both cargos engage a common Myo10 surface but also contact distinct sites. Super-resolution DNA-PAINT imaging reveals distinct patterning of cargo with Myo10 along and around filopodia. Concentration measurements show that DCC is primarily bound while β1 integrin exhibits a broader range of occupancy along the filopodial shaft. Multiple additive weak contacts and a shared binding site implies that DCC can out-compete integrin for Myo10 binding, which causes redistribution of active β1 integrin from the filopodial tip to the shaft. Our findings illustrate a tunable, multivalent binding strategy that allows Myo10 to selectively coordinate diverse signaling cargos, demonstrating how regulated disorder within IDRs is one mechanism underlying cargo binding and cellular signaling.

  PublisherDOI

• Quantifying Intracellular Distributions of HaloTag-Labeled Proteins With SDS-PAGE and Epifluorescence Microscopy

  BIO-PROTOCOL · 2025-01-01

  articleOpen accessSenior author

  Counting protein molecules helps reveal the organization of components within cellular structures and the stoichiometries of protein complexes. Existing protein and peptide quantitation methods vary in their complexity. Here, we report a straightforward workflow to measure the absolute number of HaloTag-labeled myosin 10 (Myo10) molecules in U2OS cells. Myo10 is a motor protein that plays a prominent role in cellular protrusion formation. Various biochemical and biological properties of Myo10 are established, but it is not well-defined how many molecules of Myo10 pack into narrow cellular structures called filopodia. We present a workflow for using SDS-PAGE to calibrate Myo10 signal with a reference protein, segmenting epifluorescence microscopy images to map Myo10 intracellular distribution, and interpreting the results to derive biological and functional insights. Our protocol is simple to employ and not only applicable for Myo10 research but also easily adaptable for other biological systems that use HaloTag. Key features • Combining SDS-PAGE densitometry with epifluorescence microscopy to quantitate HaloTag-labeled proteins in cells with readily available equipment. • Details for quantifying protein signal intensity in cellular compartments with semi-automated image segmentation.

  PublisherDOI

• Publisher Correction: Radiation-induced amphiregulin drives tumour metastasis

  Nature · 2025-11-10 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• BPS2025 - Intrinsically disordered regions are crucial for myosin 10 cargo binding as revealed by HDX/XL-MS and DNA-PAINT

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Radiation-induced amphiregulin drives tumour metastasis

  Nature · 2025-05-14 · 57 citations

  articleOpen access
  PublisherOA PDFDOI

• BPS2025 - Intrinsically disordered regions are crucial for myosin 10 cargo binding as revealed by HDX/XL-MS and DNA-PAINT

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Hundreds of myosin 10s are pushed to the tips of filopodia and could cause traffic jams on actin

  eLife · 2024-10-31 · 3 citations

  articleOpen accessSenior authorCorresponding

  Myosin 10 (Myo10) is a motor protein known for its role in filopodia formation. Although Myo10-driven filopodial dynamics have been characterized, there is no information about the absolute number of Myo10 molecules during the filopodial lifecycle. To better understand molecular stoichiometries and packing restraints in filopodia, we measured Myo10 abundance in these structures. We combined SDS-PAGE densitometry with epifluorescence microscopy to quantitate HaloTag-labeled Myo10 in U2OS cells. About 6% of total intracellular Myo10 localizes to filopodia, where it enriches at opposite cellular ends. Hundreds of Myo10s are in a typical filopodium, and their distribution across filopodia is log-normal. Some filopodial tips even contain more Myo10 than accessible binding sites on the actin filament bundle. Live-cell movies reveal a dense cluster of over a hundred Myo10 molecules that initiates filopodial elongation. Hundreds of Myo10 molecules continue to accumulate during filopodial growth, but accumulation ceases when retraction begins. Rates of filopodial elongation, second-phase elongation, and retraction are inversely related to Myo10 quantities. Our estimates of Myo10 molecules in filopodia provide insight into the physics of packing Myo10, its cargo, and other filopodia-associated proteins in narrow membrane compartments. Our protocol provides a framework for future work analyzing Myo10 abundance and distribution upon perturbation.

  PublisherDOI

• Author response: Pushed to the edge: hundreds of myosin 10s pack into filopodia and could cause traffic jams on actin

  2024-07-01

  peer-reviewOpen accessSenior author

  Myosin 10 (Myo10) is a motor protein well known for its role in filopodia formation. Although Myo10-driven filopodial dynamics have been characterized, there is no information about the absolute number of Myo10 molecules during the filopodial lifecycle. To better understand molecular stoichiometries and packing restraints in filopodia, we measured Myo10 abundance in these structures. Here we combined SDS-PAGE densitometry with epifluorescence microscopy to quantitate HaloTag-labeled Myo10 in U2OS cells. About 6% of total intracellular Myo10 localizes to filopodia, where it is enriched at opposite ends of the cell. Hundreds of Myo10 are found in a typical filopodium, and their distribution across filopodia is log-normal. Some filopodial tips even contain more Myo10 than accessible binding sites on the actin filament bundle. Live-cell movies reveal a dense cluster of over a hundred Myo10 molecules that initiates filopodial elongation. Hundreds of Myo10 molecules continue to accumulate during filopodial growth, but that accumulation ceases when filopodia begin to retract. Rates of filopodial elongation, second-phase elongation, and retraction are inversely related to Myo10 quantities. Our estimates of Myo10 molecules in filopodia provide insight into the physics of packing Myo10, its cargo, and other filopodia-associated proteins in narrow membrane compartments. Our protocol provides a framework for future work analyzing Myo10 abundance and distribution upon perturbation.

  PublisherOA PDFDOI

• Pushed to the edge: hundreds of myosin 10s pack into filopodia and could cause traffic jams on actin

  eLife · 2024-07-01

  preprintOpen accessSenior author

  Abstract Myosin 10 (Myo10) is a motor protein well known for its role in filopodia formation. Although Myo10-driven filopodial dynamics have been characterized, there is no information about the absolute number of Myo10 molecules during the filopodial lifecycle. To better understand molecular stoichiometries and packing restraints in filopodia, we measured Myo10 abundance in these structures. Here we combined SDS-PAGE densitometry with epifluorescence microscopy to quantitate HaloTag-labeled Myo10 in U2OS cells. About 6% of total intracellular Myo10 localizes to filopodia, where it is enriched at opposite ends of the cell. Hundreds of Myo10 are found in a typical filopodium, and their distribution across filopodia is log-normal. Some filopodial tips even contain more Myo10 than accessible binding sites on the actin filament bundle. Live-cell movies reveal a dense cluster of over a hundred Myo10 molecules that initiates filopodial elongation. Hundreds of Myo10 molecules continue to accumulate during filopodial growth, but that accumulation ceases when filopodia begin to retract. Rates of filopodial elongation, second-phase elongation, and retraction are inversely related to Myo10 quantities. Our estimates of Myo10 molecules in filopodia provide insight into the physics of packing Myo10, its cargo, and other filopodia-associated proteins in narrow membrane compartments. Our protocol provides a framework for future work analyzing Myo10 abundance and distribution upon perturbation.

  PublisherDOI

• Design and Use of AsLOV2-Based Optogenetic Tools for Actin Imaging

  Methods in molecular biology · 2024-12-26

  articleSenior author
  PublisherDOI

Recent grants

• Force-sensitive macromolecular cytoskeletal assembly

  NIH · $1.1M · 2014–2019

• Allostery in myosins studied at the molecular level

  NIH · $2.8M · 2006–2017

• The Molecular Basis for Myosin Regulation

  NIH · $1.4M · 2018–2023

Frequent coauthors

• James A. Spudich

  Stanford University

  41 shared

• Amit Mehta

  Johns Hopkins Medicine

  21 shared

• Matthias Rief

  Center for Integrated Protein Science Munich

  20 shared

• Richard E. Cheney

  University of North Carolina at Chapel Hill

  18 shared

• Mark S. Mooseker

  Yale University

  16 shared

• David S. Courson

  Old Dominion University

  11 shared

• Zeynep Ökten

  Technical University of Munich

  10 shared

• L. Stirling Churchman

  Boston VA Research Institute

  10 shared

Labs

• Rock LabPI

Education

• B.S., Chemistry

  University of Chicago

  1992

• Ph.D., Chemistry

  Caltech

  1998

• Other, Biochemistry

  Stanford University

  2004

Awards & honors

• Burroughs Wellcome Career Award at the Scientific Interface…
• Helen Hay Whitney Postdoctoral Fellow 1999