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585.709.81 - Biomechanics of Cells and Stem Cells

Applied Biomedical Engineering

Fall 2023

Description

The class starts with introductory lectures on the place of cell mechanics in the broader areas of cell biology, physiology, and biophysics, where the general topics of cell structure, motility, force generation, and interaction with the extracellular matrix are considered. The importance of the cell mechanical properties as indicators of the cell performance under normal and pathological conditions is emphasized. Major experimental techniques, such as micropipette aspiration, atomic force microscopy, and magnetic cytometry, to probe cell mechanical properties are presented. Linear elastic and viscoelastic models are introduced and applied to the interpretation of the mechanical experiments with endothelial cells and fibroblasts. Then the class discusses cell adhesion, spreading, and motility focusing on the experiments and models to estimate traction forces (stresses) produced by the cell. Finally, the effects of various mechanical factors (applied strains or forces, stiffness and viscoelastic properties, surface topography) on stem cell lineage commitment are discussed. Students also read and make presentations on original journal papers covering additional topics, which exposes them to the professional literature and hones their communication skills.

Instructor

Alexander Spector

aspector@jhu.edu

Course Structure

The course materials are divided into modules which can be accessed by clicking Course Modules on the left menu. A module will have several sections including the overview, content, readings, discussions, and assignments. You are encouraged to preview all sections of the module before starting. Most modules run for a period of seven (7) days, exceptions are noted in the Course Outline. You should regularly check the Calendar and Announcements for assignment due dates.

Course Goals

To learn the importance of mechanical forces, deformations, strain rates, adhesion, etc. to the performance of the cell under normal and pathological conditions. To learn how the mechanical properties become indicators of cellular processes, including pathological conditions, and even the stage of a disease. To show the effectiveness of cell modeling to the determination of cell mechanical properties.

Course Learning Outcomes (CLOs)

Explain how the cell mechanical properties could be indicators of a disease and its stage.
Explain the role of the mechanical properties of the extracellular matrix in the scaffold design for regenerative medicine.
Present the micropipette aspiration technique to measure the mechanical properties of suspended cells.
Present the atomic microscopy technique to measure the mechanical properties of adherent cells.
Apply mathematical models to the interpretation of experiments.
Apply the concept of complex moduli to the analysis of the time-dependent and dynamic properties of cells.
Present the magnetic cytometry techniques to measure the time-dependent and dynamic properties of cells.
Relate the cell traction forces to cell spreading, adhesion, and migration.
Explain the effect of various mechanical factors (cell spreading, substrate stiffness, substrate topography) on stem cell differentiation.

Textbooks

Required There is no required textbook for this course. Instead, Lecture Notes are provided.

Optional Additionally, the following text may be useful as additional reference material: Ethier, C. R., & Simmonds, C. A. (2007). Introductory biomechanics: From cells to organisms. Cambridge, UK: Cambridge University Press. (Chapters 1 and 2, specifically)

Other Materials & Online Resources

Lecture notes are provided on blackboard.

Required Software

MATLAB

You will need access to a recent version of MATLAB with the Signal Processing Toolkit. The MATLAB Total Academic Headcount (TAH) license is now in effect. This license is provided at no cost to you. Send an email to software@jhu.edu to request your license file/code. Please indicate that you need a standalone file/code. You will need to provide your first and last name, as well as your Hopkins email address. You will receive an email from Mathworks with instructions to create a Mathworks account. The MATLAB software will be available for download from the Mathworks site.

Student Coursework Requirements

It is expected that each module will take approximately 7–10 hours per week to complete. Here is an approximate breakdown: reading the assigned sections of the texts (approximately 3–4 hours per week) as well as some outside reading, listening to the audio annotated slide presentations (approximately 2–3 hours per week), and writing assignments (approximately 2–3 hours per week). This course will consist of the following basic student requirements:

Module Assignments (45% of Final Grade Calculation): Include your name, assignment identifier, and a page number indicator (i.e., page x of y) on each page of your submissions. Each problem should have the problem statement, assumptions, computations, and conclusions/discussion delineated. All Figures and Tables should be captioned and labeled appropriately. All assignments are due according to the dates in the Calendar. Late submissions will be reduced by one letter grade for each week late (no exceptions without prior coordination with the instructors). If, after submitting a written assignment you are not satisfied with the grade received, you are encouraged to redo the assignment and resubmit it. If the resubmission results in a better grade, that grade will be substituted for the previous grade.

Group Journal Reports (25% of Final Grade Calculation): The class will be split into several groups, and each group will work on an assigned journal paper. Together, the students of each group will prepare a written report on the journal paper and upload it for discussion with the class. There will be 2 Journal Report submissions: in Module 8 and Module 13. The Group Journal Reports are evaluated by the following grading elements, as described in the Group Journal Reports Instructions document: 1. Technical understanding of the paper (20%) 2. Relevance to the course topics (10%) 3. Quality of the report (35%) 4. Individual participation in the report discussion (35%)

MATLAB Project (30% of Final Grade Calculation): A MATLAB project will be assigned two weeks before the end of the course dealing with one of the experiments on cell (stem cell) biomechanics and applying a mathematical model for its interpretation. The last week will be devoted to the reporting of the project results. The MATLAB project is evaluated by the following grading elements, as described in the MATLAB Project Instructions document: 1. Correctness of the solution (70%) 2. MATLAB implementation (20%) 3. Presentation of the results (10%)

Grading Policy

Assignments are due according to the dates posted in your Blackboard course site. You may check these due dates in the Calendar or the Assignments in the corresponding modules. I/We will post grades one week after assignment due dates. We generally do not directly grade spelling and grammar. However, egregious violations of the rules of the English language will be noted without comment. Consistently poor performance in either spelling or grammar is taken as an indication of poor written communication ability that may detract from your grade. A grade of A indicates achievement of consistent excellence and distinction throughout the course—that is, conspicuous excellence in all aspects of assignments and discussion in every week. A grade of B indicates work that meets all course requirements on a level appropriate for graduate academic work. These criteria apply to both undergraduates and graduate students taking the course.

100-98 = A+
97-94 = A
93-90 = A−
89-87 = B+
86-83 = B
82-80 = B−
79-77 = C+
76-73 = C
72-70 = C−
69-67 = D+
66-63 = D

Academic Policies

Deadlines for Adding, Dropping and Withdrawing from Courses

Students may add a course up to one week after the start of the term for that particular course. Students may drop courses according to the drop deadlines outlined in the EP academic calendar (https://ep.jhu.edu/student-services/academic-calendar/). Between the 6th week of the class and prior to the final withdrawal deadline, a student may withdraw from a course with a W on their academic record. A record of the course will remain on the academic record with a W appearing in the grade column to indicate that the student registered and withdrew from the course.

Academic Misconduct Policy

All students are required to read, know, and comply with the Johns Hopkins University Krieger School of Arts and Sciences (KSAS) / Whiting School of Engineering (WSE) Procedures for Handling Allegations of Misconduct by Full-Time and Part-Time Graduate Students.

This policy prohibits academic misconduct, including but not limited to the following: cheating or facilitating cheating; plagiarism; reuse of assignments; unauthorized collaboration; alteration of graded assignments; and unfair competition. Course materials (old assignments, texts, or examinations, etc.) should not be shared unless authorized by the course instructor. Any questions related to this policy should be directed to EP’s academic integrity officer at ep-academic-integrity@jhu.edu.

Students with Disabilities - Accommodations and Accessibility

Johns Hopkins University values diversity and inclusion. We are committed to providing welcoming, equitable, and accessible educational experiences for all students. Students with disabilities (including those with psychological conditions, medical conditions and temporary disabilities) can request accommodations for this course by providing an Accommodation Letter issued by Student Disability Services (SDS). Please request accommodations for this course as early as possible to provide time for effective communication and arrangements.

For further information or to start the process of requesting accommodations, please contact Student Disability Services at Engineering for Professionals, ep-disability-svcs@jhu.edu.

Student Conduct Code

The fundamental purpose of the JHU regulation of student conduct is to promote and to protect the health, safety, welfare, property, and rights of all members of the University community as well as to promote the orderly operation of the University and to safeguard its property and facilities. As members of the University community, students accept certain responsibilities which support the educational mission and create an environment in which all students are afforded the same opportunity to succeed academically.

For a full description of the code please visit the following website: https://studentaffairs.jhu.edu/policies-guidelines/student-code/

Classroom Climate

JHU is committed to creating a classroom environment that values the diversity of experiences and perspectives that all students bring. Everyone has the right to be treated with dignity and respect. Fostering an inclusive climate is important. Research and experience show that students who interact with peers who are different from themselves learn new things and experience tangible educational outcomes. At no time in this learning process should someone be singled out or treated unequally on the basis of any seen or unseen part of their identity.

If you have concerns in this course about harassment, discrimination, or any unequal treatment, or if you seek accommodations or resources, please reach out to the course instructor directly. Reporting will never impact your course grade. You may also share concerns with your program chair, the Assistant Dean for Diversity and Inclusion, or the Office of Institutional Equity. In handling reports, people will protect your privacy as much as possible, but faculty and staff are required to officially report information for some cases (e.g. sexual harassment).

Course Auditing

When a student enrolls in an EP course with “audit” status, the student must reach an understanding with the instructor as to what is required to earn the “audit.” If the student does not meet those expectations, the instructor must notify the EP Registration Team [EP-Registration@exchange.johnshopkins.edu] in order for the student to be retroactively dropped or withdrawn from the course (depending on when the "audit" was requested and in accordance with EP registration deadlines). All lecture content will remain accessible to auditing students, but access to all other course material is left to the discretion of the instructor.