Dr. Ryan Littlefield's Research Area
Areas of interest
- Hypothesis-driven research on self-organization and dynamics of striated muscle and other contractile structures.
- High-resolution microscopy and structural modeling
- Visualization techniques using physical models
- Bioengineering of muscle scaffolds
- Nebulin does not specify actin lengths
A New Paradigm for Striated Muscle
- Actin is dynamic in striated muscle
- Nebulin does not specify actin lengths
- Only found in vertebrate skeletal muscle and only extends along 90-95% of the actin filament.
- Not found within striated invertebrate muscles
- Actin is dynamic in striated muscle
- Actin subunits exchange more at the pointed (P-) ends than the barbed (B-) ends, even though P-ends grow slower in vitro.
- Precise lengths are specified by regulated exchange of subunits at the P-ends.
- Our Working Hypothesis: Titin and the myosin thick filaments form a scaffold that
specifies actin filament lengths
- This ensures full overlap between actin and myosin and maximal force generation
Recent Publications
Refereed Publications:
Littlefield, R., Almenar-Queralt, A., and V. M. Fowler, 2001. Actin Dynamics at Pointed Ends Regulates Thin Filament Length in Striated Muscle. Nature Cell Biology, 3:544-551.
Littlefield, R. and V. M. Fowler, 2002. Measurement of Thin Filament Lengths by Distributed Deconvolution Analysis of Fluorescence Images. Biophysical Journal, 82:2548-64.
Nolen, B. J.†, Littlefield, R. S.†, and T. D. Pollard, 2004. Crystal structures of actin-related protein 2/3 complex with bound ATP or ADP. Proc. Natl. Acad. Sci. U S A, 101:15627-32. F1000 († co-first authors)
Bang, M.-L., Li, X., Littlefield, R., Bremner, S., Thor, A., Knowlton, K. U., Lieber, R. L., and J. Chen, 2006. Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle. J. Cell Biol., 173:905-16. F1000
Rajasekaran, M. R., Jiang, Y., Bhargava, V., Littlefield, R., Lee, A., Lieber, R. L., and R. K. Mittal, 2008. Length-Tension Relationship of the External Anal Sphincter Muscle: Implications for the Anal Canal Function. Am. J. Physiol. Gastrointest. Liver Physiol., 295:G367-73.
Castillo, A. M., Nowak, R. B., Littlefield, K. P., Fowler, V. M., and R. S. Littlefield, 2009. A Nebulin Ruler Does Not Dictate Thin Filament Lengths. Biophysical Journal, 96:1856-65. F1000
Bang, M.-L., Caremani, M., Brunello, E., Littlefield, R., Lieber, R., Chen, J., Lombardi, V., and M. Linari, 2009. Nebulin Plays a Direct Role in Promoting Strong Actin-Myosin Interactions, FASEB Journal, 23:4117-25.
Gokhin, D. S., Lewis, R. A., McKeown, C. R., Nowak, R. B., Kim, N. E., Littlefield, R. S., Lieber, R. L., and V. M. Fowler, 2010. Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology. J. Cell Biol., 189:95-109.
Littlefield, R., Amann, K., Gokhin, D. S., and V. M. Fowler. Differential Incorporation of Labeled Actin into Striated Myofibrils, in preparation for Cytoskeleton.
Non-Refereed Publications:
Littlefield, R. and V. M. Fowler, 1998. Defining Actin Filament Length in Striated Muscle: Rulers and Caps or Dynamic Stability? Ann. Rev. Cell Dev. Biology, 14:487-525.
Littlefield, R. and V. M. Fowler, 2002. Cytoskeleton: A (Minor) Actin Catastrophe. (News and Views) Nature Cell Biology, 4:E209-11.
Wittman, T., Littlefield, R., and C. M. Waterman-Storer, 2004. Fluorescent Speckle Microscopy of Cytoskeletal Dynamics in Living Cells. pg. 187-204. In R. D. Goldman & D. L. Spector (Eds.), Live Cell Imaging: A Laboratory Manual, Cold Spring Harbor Laboratory Press.
Littlefield, R. S., and V. M. Fowler, 2008. Thin Filament Length Regulation In Striated Muscle Sarcomeres: Pointed-End Dynamics Go Beyond A Nebulin Ruler. Seminars in Cell and Developmental Biology, 19:511-519.
F1000 Recommended article at Faculty of 1000