Crosslisted as: MCEN 4228/5228; CHEM 4751/5751; PHYS 7810-004/4810-001
Instructor: Thomas Perkins, tperkins@jila.colorado.edu
Straightforward application of classical Newtonian physics does a poor job of providing insight into biological processes. This course will develop a simple description of the biophysics governing the motion of molecules inside of cells. This course starts with an overview of the physics that governs molecular motors, the cytoskeleton and, more generally, proteins inside of the cell as well as a review of single molecule techniques. Topics covered will include diffusion, entropy, chemical energy, polymers, intermolecular forces, cytoskeleton, molecular motors, and single-molecule techniques. Each student will give two oral presentations on journal articles. Problem sets will provide a quantitative understanding of the topics discussed. A final paper will be required that addresses a critical question in biophysics and/or outlines a proposed experimental approach to answer the question, or a design project to address a biomedical application.
Prereq, CHEM 1131 or 1171, physics 2010, 2020, MCDB 3120, or instructor consent.
Recommended prereq., Math 1300 and/or CHEM 3311. Same as MCDB 5550.
Grade determination:
15% Participation in class discussion
30% Oral presentation
25% Problem sets
30% Final paper
Presentations:
Each student will give two oral presentations, in teams if necessary, on the primary literature reading assignments. These presentations will be followed by a discussion led by the presenting student(s) to critically analyze the reading material and to review what students have learned from the presentation and the reading material.
Paper:
Each student will write a 6-8 page paper (10-12 for graduate students) that either proposes (i) an experiment using biophysical techniques with quantitative estimates, (ii) a critique of a set of papers, (iii) a design project (upon approval by an instructor) or (iv) a topic mutually agreed upon between the student and an instructor. Paper is due April 28th by 5 PM.
Texts (required for course):
Mechanics of Motor Proteins and the Cytoskeleton by Jonathon Howard, 2001
Texts (supplementary information):
- Molecular Biology of the Cell 54th Edition, silver cover), By Alberts, et al., (any addition)
--A good, encyclopedic biology text book. Very good for learning vocabulary but a little dry - Biochemistry (7th Edition, grey cover), By Berg, Tymoczko, Stryer, &, 2010 or equivalent
- Physical Biology of the Cell, 2nd Edition, Phillips et al. (Excellent but more advanced)
Office Hours
Time: Wednesday 2-3 pm
Office: JILA A503 or zoom (Meeting ID: 942 0224 5122; Passcode distributed by email, same as class zoom.
Syllabus
Week |
Tuesday |
Thursday |
1: 1/11-13 |
Introduction |
Random walks & mechanical forces |
2: 1/18-20 |
Mass, stiffness & damping of a protein |
Single Molecule Techniques: Optical Traps and applications to molecular motors (Perkins, 2009, & Perkins, 2014) (HW#2 due 1/27/2022) |
3: 1/25-27 |
Cytoskeletal filaments Reading: Chapter 7 |
Motor proteins Reading: Chapters 12-13 |
4: 2/1-3 |
Thermal forces & diffusion |
Chemical forces |
5: 2/8-10 |
Points on presenting a scientific paper |
Presentation example: Hua et al., Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements (HW#4 due 2/17/2022) |
6: 2/15-17 |
Single Molecule Techniques: Fluorescence |
Group 1 Presentation: Asbury et al, Kinesin moves by an asymmetry is hand over hand mechanism (HW #5 due 2/24/2022) |
7: 2/22-24 |
Single molecule techniques: Atomic Force microscopy |
Group 2 Presentation: Yildiz et al Kinesin walks hand over hand |
8: 3/1-3 |
Single molecule techniques: Magnetic tweezers (Neuman et al, 2008), |
Cytoskeletal filament mechanics and polymerization Reading: Chapters 8-9 |
9: 3/8-10 |
Guest lecture: Erik Schaeffer. High resolution stepping of kinesin |
Nanomechanics DNA and nucleic acid hairpins (Chapter 6) (HW #7 due March 17) |
10: 3/15-17 |
Group 3 Presentation: Group 3: Wang & Ha, Defining single molecular forces required to activate integrin and notch signaling |
Group 4 Presentation: Zhang, et al., DNA-based digital tension probes reveal integrin forces during early cell adhesion (HW #8 due 3/31/2022) |
3/22-24 |
Spring Break |
Spring Break |
11: 3/29-31 |
Polymerization Reading: Chapters 9-10 |
Group 1 Presentation: Kerssemakers et al, Assembly dynamics of microtubules at molecular resolution (HW #9 due 4/7/2022) |
12: 4/5-7 |
Active polymerization Reading: Chapters 11 |
Group 2 Presentation: Asbury et al., Dam1 kinetochore complex harnesses microtubule dynamics to produce force and movement (HW #10 due 4/14/2022) |
13: 4/12-14 |
ATP Hydrolysis Reading Chap 14 |
Group 3 Presentation: LeBlanc et al., Type III secretion system effector proteins are mechanically labile(HW #11 due 4/21/2022) |
14: 4/19-21 |
Steps, forces, and motility models Reading: Chapter 15-16 |
Group 4 Presentation: Zhao & Woodside, Mechanical strength of RNA know in Zika virus protects against cellular defenses
|
15: 4/26-28 |
Guest Lecture: Dick McIntosh
|
Summary: |
CLASSROOM BEHAVIOR
Both students and faculty are responsible for maintaining an appropriate learning environment in all instructional settings, whether in person, remote or online. Those who fail to adhere to such behavioral standards may be subject to discipline. Professional courtesy and sensitivity are especially important with respect to individuals and topics dealing with race, color, national origin, sex, pregnancy, age, disability, creed, religion, sexual orientation, gender identity, gender expression, veteran status, political affiliation or political philosophy. For more information, see the policies on classroom behavior and the Student Conduct & Conflict Resolution policies.
REQUIREMENTS FOR COVID-19
As a matter of public health and safety, all members of the CU Boulder community and all visitors to campus must follow university, department and building requirements and all public health orders in place to reduce the risk of spreading infectious disease. Students who fail to adhere to these requirements will be asked to leave class, and students who do not leave class when asked or who refuse to comply with these requirements will be referred to Student Conduct and Conflict Resolution. For more information, see the policy on classroom behavior and the Student Code of Conduct. If you require accommodation because a disability prevents you from fulfilling these safety measures, please follow the steps in the “Accommodation for Disabilities” statement on this syllabus.
CU Boulder currently requires masks in classrooms and laboratories regardless of vaccination status. This requirement is a precaution to supplement CU Boulder’s COVID-19 vaccine requirement. Exemptions include individuals who cannot medically tolerate a face covering, as well as those who are hearing-impaired or otherwise disabled or who are communicating with someone who is hearing-impaired or otherwise disabled and where the ability to see the mouth is essential to communication. If you qualify for a mask-related accommodation, please follow the steps in the “Accommodation for Disabilities” statement on this syllabus. In addition, vaccinated instructional faculty who are engaged in an indoor instructional activity and are separated by at least 6 feet from the nearest person are exempt from wearing masks if they so choose.
If you feel ill and think you might have COVID-19, if you have tested positive for COVID-19, or if you are unvaccinated or partially vaccinated and have been in close contact with someone who has COVID-19, you should stay home and follow the further guidance of the Public Health Office (contacttracing@colorado.edu). If you are fully vaccinated and have been in close contact with someone who has COVID-19, you do not need to stay home; rather, you should self-monitor for symptoms and follow the further guidance of the Public Health Office (contacttracing@colorado.edu). Please email me at tperkins@jila.colorado.edu to inform me.
ACCOMMODATION FOR DISABILITIES
If you qualify for accommodations because of a disability, please submit your accommodation letter from Disability Services to your faculty member in a timely manner so that your needs can be addressed. Disability Services determines accommodations based on documented disabilities in the academic environment. Information on requesting accommodations is located on the Disability Services website. Contact Disability Services at 303-492-8671 or dsinfo@colorado.edu for further assistance. If you have a temporary medical condition, see Temporary Medical Conditions on the Disability Services website.
PREFERRED STUDENT NAMES AND PRONOUNS
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HONOR CODE
All students enrolled in a University of Colorado Boulder course are responsible for knowing and adhering to the Honor Code academic integrity policy. Violations of the Honor Code may include, but are not limited to: plagiarism, cheating, fabrication, lying, bribery, threat, unauthorized access to academic materials, clicker fraud, submitting the same or similar work in more than one course without permission from all course instructors involved, and aiding academic dishonesty. All incidents of academic misconduct will be reported to the Honor Code (honor@colorado.edu; 303-492-5550). Students found responsible for violating the academic integrity policy will be subject to nonacademic sanctions from the Honor Code as well as academic sanctions from the faculty member. Additional information regarding the Honor Code academic integrity policy can be found on the Honor Code website.
SEXUAL MISCONDUCT, DISCRIMINATION, HARASSMENT AND/OR RELATED RETALIATION
CU Boulder is committed to fostering an inclusive and welcoming learning, working, and living environment. The university will not tolerate acts of sexual misconduct (harassment, exploitation, and assault), intimate partner violence (dating or domestic violence), stalking, or protected-class discrimination or harassment by or against members of our community. Individuals who believe they have been subject to misconduct or retaliatory actions for reporting a concern should contact the Office of Institutional Equity and Compliance (OIEC) at 303-492-2127 or email cureport@colorado.edu. Information about university policies, reporting options, and the support resources can be found on the OIEC website.
Please know that faculty and graduate instructors have a responsibility to inform OIEC when they are made aware of incidents of sexual misconduct, dating and domestic violence, stalking, discrimination, harassment and/or related retaliation, to ensure that individuals impacted receive information about their rights, support resources, and reporting options. To learn more about reporting and support options for a variety of concerns, visit Don’t Ignore It.
RELIGIOUS HOLIDAYS
Campus policy regarding religious observances requires that faculty make every effort to deal reasonably and fairly with all students who, because of religious obligations, have conflicts with scheduled exams, assignments or required attendance. In this class, please inform me at least two weeks ahead of time, paying particular attention to when you are working as a group.
See the campus policy regarding religious observances for full details.