Interdisciplinary PhD program in Structural and Computational Biology and Quantitative Biosciences

Jacob Notbohm

Harvey D. Spangler Assistant Professor, Department of Engineering Physics Lab Website jknotbohm@wisc.edu(608) 890-0030

533 Engineering Research Building
1500 Engineering Drive
Madison, WI 53706-1609

Education

B.S., University of Wisconsin-Madison
M.S., California Institute of Technology
Ph.D., California Institute of Technology

How biological cells adhere, push, pull, and move, using mechanics, soft matter physics, applied math, and cell biology

MECHANICS OF FIBROUS MATERIALS

Biological tissues are primarily composed of networks of fibers with lengths on the order of a micron. These fibrous materials have an important mechanical role in maintaining human health, because they provide macroscale structure for tissues and microscale cues that guide cell behavior.

The mechanics of fibrous materials are complicated. When stress is applied to these fibrous materials, their deformations are heterogeneous and vary nonlinearly with the applied stress. We study how the fibrous structure brings about these complicated mechanical properties. Much of our research focuses on the response of these materials to complicated localized forces, similar to the forces applied by a cell as it contracts or migrates. Our research methods use a combination of computational simulations and novel experiments.

FIBER-SCALE DISPLACEMENTS IN FIBROUS MATERIALS

We produce local displacements in fibrous materials by embedding a particle made of an active gel whose contraction we control. Imaging under the microscope allows us to compute displacements at the scale of the fibers.

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Fibrous network of collagen around contracting particle. Image source: Burkel and Notbohm, Soft Matter, 13:5749-5758 (2017).

colormap of displacements in fibrous material

Displacements induced by contracting particle.

FIBER NETWORK MODEL

Using finite element software, we model each fiber in the network as a beam that can bend, stretch, and buckle. Solutions from the model are compared to experimental data.

Fiber network model in bending. Image source: Tyznik and Notbohm, Mechanics of Materials, 138:103155 (2019).

COLLECTIVE CELL MIGRATION

Cells migrate in collective groups in tissue development, wound healing, and cancer metastasis. We study the mechanics of collective migration with the goal of identifying relationships between the active forces produced by each cell and the motion of the cell collective. Our experimental methods integrate cell culture with optical microscopy and quantitative image analysis.

TRACKING CELL MOTION

Using quantitative image analysis, we quantify the cell motion, as shown by the lines showing the trajectory of each cell on the right.

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EXPANSION OF A CELL ISLAND

A typical experiment to simulate wound healing studies cell migration into free space. Shown below is an example, with color plots indicating tractions exerted by the cells to the substrate beneath them and the stresses applied by the cells to their neighbors.

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Areas of Expertise

  • Membrane & Cellular Biophysics
  • Spectroscopy Microscopy Imaging