Picture of Wesley Wong
Wesley Philip Wong, Ph.D.
Associate Professor of Biological Chemistry and Molecular Pharmacology

We are interested in understanding the physical basis of how biological systems work at the nanoscale, with a focus on the role of mechanical force.


We are interested in understanding the physical basis of how biological systems work at the nanoscale, with a focus on the role of mechanical force. More specifically, we investigate how force regulates the structure and dynamics of interactions between and within single-molecules, and how this in turn can affect the functioning and malfunctioning of biological systems. To accomplish this, my group develops and applies novel tools in single-molecule manipulation and detection, combining approaches from a variety of disciplines, including physics, molecular biology, chemistry, and engineering. Some key research projects that we are working on are highlighted below.

1. Novel high-throughput methods in single-molecule manipulation, including single-molecule centrifugation

The precise manipulation and observation of single molecules provides a detailed view of biomolecular systems that is unobscured by ensemble averaging, and that reveals non-equilibrium and force-dependent behavior. However, widespread adoption of single-molecule techniques has been impeded by equipment cost and the laborious nature of making measurements one molecule at a time. My group is developing a new approach to solve these issues: massively parallel single-molecule force measurements using centrifugal force. Our new instrument, the Centrifuge Force Microscope (CFM), can perform thousands of single-molecule force experiments in parallel, enabling measurements to be made in minutes rather than in days.

Drawing from techniques ranging from optical tweezers and single-molecule fluorescence to modern methods in molecular biology and surface/linkage chemistry, my group develops novel approaches as needed to answer interesting biological and biophysical questions.

2. Force-regulated molecular interactions in the circulatory system, including studies on the vascular protein von Willebrand factor

Molecules in the circulatory system operate in a dynamic environment of forces and flow. This is particularly true for vascular molecules involved in cell adhesion. Single-molecule force studies give us a way to understand how these molecular systems work, by serving as both an analogue for forces experienced in the body, and as a probe for exploring the interaction energy landscape.

We have been studying the vascular protein von Willebrand Factor (vWF), which is responsible for tethering platelets both to each other and to sites of trauma under conditions of high shear. For example, in collaboration with Timothy A. Springer’s group we have shown that the A2 domain of vWF functions as a force-activated single-molecule switch in a key molecular feedback loop that regulates primary hemostasis. Specifically, by characterizing the kinetics of this system using single-molecule force spectroscopy, we have shown that hydrodynamic forces in the circulation can act as a “cofactor” for enzymatic cleavage of A2 by the ADAMTS13 enzyme. We are continuing to investigate the dynamics of molecular transitions within vWF (e.g. bond formation and rupture, unfolding/refolding transitions, and enzymatic cleavage) under conditions of externally applied tension and hydrodynamic flow, which should lead to new insights into von Willebrand disease, the most common hereditary bleeding disorder.

3. Other studies on the role of mechanical force in nanoscale biology, include:

a) Structure and dynamics of bacterial chromosomes
b) Development of force-based nanoscale molecular therapeutics
c) Dynamics of Actin-associated proteins
d) Development of quantitative models and methods of analysis for biomolecular interactions


Center for Life Sciences Bldg, 3rd floor

3 Blackfan Circle

Boston, MA 02115

Publications View
Small but Mighty: Nanoparticles Probe Cellular Signaling Pathways.
Authors: Authors: Yang D, Wong WP.
Dev Cell
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Multiplexed single-molecule force spectroscopy using a centrifuge.
Authors: Authors: Yang D, Ward A, Halvorsen K, Wong WP.
Nat Commun
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DNA nanoswitches: a quantitative platform for gel-based biomolecular interaction analysis.
Authors: Authors: Koussa MA, Halvorsen K, Ward A, Wong WP.
Nat Methods
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Protocol for sortase-mediated construction of DNA-protein hybrids and functional nanostructures.
Authors: Authors: Koussa MA, Sotomayor M, Wong WP.
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Bioinspired multivalent DNA network for capture and release of cells.
Authors: Authors: Zhao W, Cui CH, Bose S, Guo D, Shen C, Wong WP, Halvorsen K, Farokhzad OC, Teo GS, Phillips JA, Dorfman DM, Karnik R, Karp JM.
Proc Natl Acad Sci U S A
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Physical manipulation of the Escherichia coli chromosome reveals its soft nature.
Authors: Authors: Pelletier J, Halvorsen K, Ha BY, Paparcone R, Sandler SJ, Woldringh CL, Wong WP, Jun S.
Proc Natl Acad Sci U S A
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Binary DNA nanostructures for data encryption.
Authors: Authors: Halvorsen K, Wong WP.
PLoS One
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Nanoengineering a single-molecule mechanical switch using DNA self-assembly.
Authors: Authors: Halvorsen K, Schaak D, Wong WP.
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Massively parallel single-molecule manipulation using centrifugal force.
Authors: Authors: Halvorsen K, Wong WP.
Biophys J
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Note: High-precision microsphere sorting using velocity sedimentation.
Authors: Authors: Cheng D, Halvorsen K, Wong WP.
Rev Sci Instrum
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