An understanding of the locomotion of animals is of great practical and scientific importance. Despite much effort, many questions remain unanswered regarding the effects of fluid rheology (e.g. viscoelasticity) on the motility of small living organisms. Answers to these questions can lead to potentially useful applications spanning many fields such as engineering, robotics, physics, and biology. For example, motility investigations of model living organisms can provide a powerful tool for the analysis of new and existing mutations involved in Muscular Dystrophy (MD), a disease that affects millions of people worldwide but, to date, has no cure. This project aims to (1) advance our understanding of the forces governing nematode motility in complex media including viscoelastic fluids and to (2) measure non-invasively the biomechanical and material properties of healthy and mutant nematodes carrying MD. The organism of choice is the nematode (worm) Caenorhabditis (C.) elegans, which is a promising candidate for motility investigations at low Reynolds numbers in complex fluids due to their small size (L~ 1 mm) and adaptability to various fluidic environments. C. elegans is also a model biological system used to explore potential causes and treatments for human diseases because their genome has been completely sequenced. In addition, the motility of C. elegans is controlled by 95 muscle cells that are highly similar in both anatomy and molecular makeup to vertebrate skeletal muscle. These muscle cells express many genes associated with human muscular dystrophies, such as genes homologous to Dystrophin and (Duchennes MD) and Dysferlin (Limb Girdle MD). This research is motivated by two primary objectives. The first is devoted to the fundamental investigation of the effects of fluids that exhibit both solid and fluid-like behavior such as viscoelastic fluids on the motility of C. elegans in the low Reynolds numbers regime. Many relevant living organisms move in viscoelastic fluids such as mucus, and bio-molecular fluids, and suspensions. However, little is known about the effects of elastic stresses on the motility behavior of living organisms. Important questions include: (i) how do fluid elastic stresses affect the motility kinematic and swimming behavior of nematodes at low Reynolds numbers? (ii) Do nematodes swim faster or slower in the presence of elastic stresses and/or shear rate dependent viscosity? (iii) Do nematodes adjust or adapt to their fluidic environment by changing their swimming gaits such as frequency and amplitude? The second involves applying this knowledge to estimate the biomechanical and material properties of swimming nematodes. By estimating such properties, the PI will be able to phenotype wild-type and mutant nematodes carrying MD, which ultimately will contribute to developing quantitative, reliable diagnostic tools for MD.

Intellectual Merit:

The research is based on the PI's previous efforts in understanding complex fluid flow phenomena, and will make new valuable contributions that are both fundamental and applied. From a fundamental perspective, the PI will (1) use high spatial and temporal resolution experiments to characterize the flow behavior and nematode motion in complex fluidic environments. Such a quantitative, engineering based analysis of muscle function provides a new paradigm for the study of muscle physiology and other diseases; (2) develop theoretical and numerical models to characterize the biomechanics of nematodes in order to non invasively obtain estimates of their material properties; and (3) investigate the effects of fluid rheological properties on the motility of nematodes. From an applied perspective, the PI will develop diagnostic tools capable of quantitatively investigating nematodes carrying genetic mutations including those associated with Muscular Dystrophy. Since C. elegans offer many advantages for defining the molecular basis of environmental stress signaling, this research program will contribute to a better understanding of motility based diseases such as Muscular Dystrophy.

Broader Impact:

An integrated research and educational program lies at the rich interface between (fluid) mechanics and biology. It includes: (1) recruiting undergraduate students for summer research internships from Historically Black Colleges and Universities that do not possess an engineering graduate program. One of the main objectives is to increase the participation of historically under represented minorities such as African Americans, Native Americans, and Hispanics in research; (2) training graduate students by offering new graduate level courses in complex and bio-fluids as well as research opportunities; (3) involving K-12 teachers in the research and educational program. Finally, the results of this research and educational program will be broadly disseminated and will have potentially important benefits to society. In particular, the results will increase understanding of new fluid mechanics phenomena and certain types of diseases.

Project Start
Project End
Budget Start
2010-07-01
Budget End
2015-06-30
Support Year
Fiscal Year
2009
Total Cost
$400,000
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104