Boards, Advisory Committees, Professional Organizations

  • Member, The Biophysical Society (2008 - Present)

Professional Education

  • Doctor of Philosophy, Stanford University, Physics (2013)
  • Master of Science, Ecole Centrale Paris, Engineering Physics (2007)
  • Master of Science, Royal Institute of Technology, Engineering Physics (2006)

Lab Affiliations

All Publications

  • The Mechanochemical Cycle of Mammalian Kinesin-2 KIF3A/B under Load CURRENT BIOLOGY Andreasson, J. O., Shastry, S., Hancock, W. O., Block, S. M. 2015; 25 (9): 1166-1175


    The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains and not to the neck linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.

    View details for DOI 10.1016/j.cub.2015.03.013

    View details for Web of Science ID 000353999000023

    View details for PubMedID 25866395

  • Examining kinesin processivity within a general gating framework. eLife Andreasson, J. O., Milic, B., Chen, G., Guydosh, N. R., Hancock, W. O., Block, S. M. 2015; 4


    Kinesin-1 is a dimeric motor that transports cargo along microtubules, taking 8.2-nm steps in a hand-over-hand fashion. The ATP hydrolysis cycles of its two heads are maintained out of phase by a series of gating mechanisms, which lead to processive runs averaging ~1 μm. A key structural element for inter-head coordination is the neck linker (NL), which connects the heads to the stalk. To examine the role of the NL in regulating stepping, we investigated NL mutants of various lengths using single-molecule optical trapping and bulk fluorescence approaches in the context of a general framework for gating. Our results show that, although inter-head tension enhances motor velocity, it is crucial neither for inter-head coordination nor for rapid rear-head release. Furthermore, cysteine-light mutants do not produce wild-type motility under load. We conclude that kinesin-1 is primarily front-head gated, and that NL length is tuned to enhance unidirectional processivity and velocity.

    View details for DOI 10.7554/eLife.07403

    View details for PubMedID 25902401

  • Kinesin processivity is gated by phosphate release PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Milic, B., Andreasson, J. O., Hancock, W. O., Block, S. M. 2014; 111 (39): 14136-14140
  • A universal pathway for kinesin stepping NATURE STRUCTURAL & MOLECULAR BIOLOGY Clancy, B. E., Behnke-Parks, W. M., Andreasson, J. O., Rosenfeld, S. S., Block, S. M. 2011; 18 (9): 1020-U79


    Kinesin-1 is an ATP-driven, processive motor that transports cargo along microtubules in a tightly regulated stepping cycle. Efficient gating mechanisms ensure that the sequence of kinetic events proceeds in the proper order, generating a large number of successive reaction cycles. To study gating, we created two mutant constructs with extended neck-linkers and measured their properties using single-molecule optical trapping and ensemble fluorescence techniques. Owing to a reduction in the inter-head tension, the constructs access an otherwise rarely populated conformational state in which both motor heads remain bound to the microtubule. ATP-dependent, processive backstepping and futile hydrolysis were observed under moderate hindering loads. On the basis of measurements, we formulated a comprehensive model for kinesin motion that incorporates reaction pathways for both forward and backward stepping. In addition to inter-head tension, we found that neck-linker orientation is also responsible for ensuring gating in kinesin.

    View details for DOI 10.1038/nsmb.2104

    View details for Web of Science ID 000294551200010

    View details for PubMedID 21841789

  • AN OPTICAL APPARATUS FOR ROTATION AND TRAPPING METHODS IN ENZYMOLOGY, VOL 475: SINGLE MOLECULE TOOLS, PT B Gutierrez-Medina, B., Andreasson, J. O., Greenleaf, W. J., Laporta, A., Block, S. M. 2010; 475: 377-404


    We present details of the design, construction, and testing of a single-beam optical tweezers apparatus capable of measuring and exerting torque, as well as force, on microfabricated, optically anisotropic particles (an "optical torque wrench"). The control of angular orientation is achieved by rotating the linear polarization of a trapping laser with an electro-optic modulator (EOM), which affords improved performance over previous designs. The torque imparted to the trapped particle is assessed by measuring the difference between left- and right-circular components of the transmitted light, and constant torque is maintained by feeding this difference signal back into a custom-designed electronic servo loop. The limited angular range of the EOM (+/-180 degrees ) is extended by rapidly reversing the polarization once a threshold angle is reached, enabling the torque clamp to function over unlimited, continuous rotations at high bandwidth. In addition, we developed particles suitable for rotation in this apparatus using microfabrication techniques. Altogether, the system allows for the simultaneous application of forces (approximately 0.1-100 pN) and torques (approximately 1-10,000 pN nm) in the study of biomolecules. As a proof of principle, we demonstrate how our instrument can be used to study the supercoiling of single DNA molecules.

    View details for DOI 10.1016/S0076-6879(10)75015-1

    View details for Web of Science ID 000280733800015

    View details for PubMedID 20627165

  • Precision steering of an optical trap by electro-optic deflection OPTICS LETTERS Valentine, M. T., Guydosh, N. R., Gutierrez-Medina, B., Fehr, A. N., Andreasson, J. O., Block, S. M. 2008; 33 (6): 599-601


    We designed, constructed, and tested a single-beam optical trapping instrument employing twin electro-optic deflectors (EODs) to steer the trap in the specimen plane. Compared with traditional instruments based on acousto-optic deflectors (AODs), EOD-based traps offer a significant improvement in light throughput and a reduction in deflection-angle (pointing) errors. These attributes impart improved force and position resolution, making EOD-based traps a promising alternative for high-precision nanomechanical measurements of biomaterials.

    View details for Web of Science ID 000254907500023

    View details for PubMedID 18347722