Date

Topic(s)

Readings, notes, handouts, etc.

1

1/23/14

2

1/27/14

Receptor-Ligand Binding Continued

Lauffenburger p1-38, skim 39-64
(In-class exercise)

3

1/30/14

R-L Binding -- Endocytosis, Trafficking, and Recycling

Lauffenburger p73-100, skim 100-122

4

2/3/14

Endocytosis and Trafficking: Everybody needs Iron

1) [OPTIONAL BACKGROUND READING] Ponka and Lok, "The transferrin receptor: role in health and disease" (good if you model FN for Project 1)
2) Sheff et al., "The Receptor Recycling Pathway Contains Two Distinct Populations of Early Endosomes with Different Sorting Functions"

5

2/6/14

1) read everything about leukocyte adhesion moledules and rolling at http://bme.virginia.edu/ley/
2. Lawrence et al., "Effect of Flow on Polymorphonuclear Leukocyte / Endothelial Cell Adhesion"
3.Eniola et al. "Interplay between Rolling and Firm Adhesion Elucidated with a Cell-Free System Engineered with Two Distinct Receptor-Ligand Pairs" [SKIM the validation parts. focus on results.]

(Discuss Project 1 Progress)

6

2/10/14

Leukocyte Rolling: Models

1)Hammer & Apte, "Simulation of cell rolling and adhesion on surfaces in shear flow"
2) [focus on part on rate constants, p60-61, while reading first Hammer paper to get background] The reaction-limited kinetics of membrane-to-surface adhesion and detachment
3) [very optional background] A DYNAMICAL MODEL FOR RECEPTOR-MEDIATED CELL ADHESION TO SURFACES
4) [very optional background] Models for the Specific Adhesion of Cells to Cells

7

2/13/14

Overview of cytoskeleleton and measurements of stiffness and traction

Overview of measurement techniques and things to come

1)(SKIM) Historical perspective on airway smooth muscle: the saga of a frustrated cell

Project 1 Due

(Start looking at Project 2)

2/17/14

President's Day -- No Class

8

2/18/14

CSK stiffness: laser traps and adhesion strengthening

1) Choquet, "Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages "
2) Jiang, "Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin"

9

2/20/14

Traction Force measurements

Project 2 Topics Due

1) Dembo & Wang, "Stresses at the Cell-to-Substrate Interface during Locomotion of Fibroblasts"
2) Tan, et al. "Cells Lying on a Bed of Microneedles"
3) (SKIM) Reinhart-King, et al., "The Dynamics and Mechanics of Endothelial Cell Spreading"

10

2/24/14

Force Measurements in 3D gels

1. Fibroblast Contractile Force Is Independent of the Stiffness Which Resists the Contraction
2. An Anisotropic Biphasic Theory of Tissue-Equivalent Mechanics: The Interplay Among Cell Traction, Fibrillar Network Deformation, Fibril Alignment, and Cell Contact Guidance

2/27/14

Mystery No Class Day

Project 2 Draft Due via email

11

3/3/14

Bringing it all together: Cadherins and Ena/VASP

1) Vascular Endothelial-Cadherin Regulates Cytoskeletal Tension, Cell Spreading, and Focal Adhesions by Stimulating RhoA
2) (SKIM) Ena/VASP is required for endothelial barrier function in vivo
3) VASP involvement in force-mediated adherens junction strengthening

12

3/6/14

Balance of Forces during Capillary Morphogenesis (Alisha presents)

1) The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro
2) The Stiffness of Three-dimensional Ionic Self-assembling Peptide Gels Affects the Extent of Capillary-like Network Formation
3) Primary sequence of ionic self-assembling peptide gels affects endothelial cell adhesion and capillary morphogenesis

Project 2 Due

13

3/10/14

Project 3 Prep day

1) [OPTIONAL BACKGROUND] A self-assembling peptide matrix used to control stiffness and binding site density supports the formation of microvascular networks in three dimensions
2) [OPTIONAL BACKGROUND] Grant proposal
3) [OPTIONAL BACKGROUND] Pericellular Conditions Regulate Extent of Cell-Mediated Compaction of Collagen Gels
4) Cell culture protocols and cell culture are in Public\+Courses\Bioengineering\Protocols\Cellular_BioE

Start Disucssing Project 3

14

3/13/14

Project 3 Working Day

Experimental Design and cell culture

15

3/24/14

Project 3 Working Day

Lab Time

16

3/27/14

Project 3 Working Day

17

3/31/14

Project 3 Working Day

Lab Time

18

4/3/14

Intro to Migration

1) you will get to see the infamous migration dance, don't miss it
2) [Background reading] Lauffenburger book, pages 302-346,
[OPTIONAL additional background reading] Cell Migration: A Physically Integrated Molecular Process
3) Pelham and Wang, “Cell locomotion and focal adhesions are regulated by substrate flexibility,”.
4) Lo, Cell Movement Is Guided by the Rigidity of the Substrate

Project 3 DRAFT DUE

19

4/7/14

2D Migration - Stiffness and Adhesion

1. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness
2. "Extracellular Matrix Rigidity Governs Smooth Muscle Cell Motility in a Biphasic Fashion"

20

4/10/14

Migration is like diffusion

1. [SKIM FOR BACKGROUND] Optimal estimation of cell movement indices from the statistical analysis of cell tracking data
2. Directional Persistence of EGF-Induced Cell Migration Is Associated
with Stabilization of Lamellipodial Protrusions
3. Temporal Variations in Cell Migration and Traction during Fibroblast-Mediated Gel Compaction

Project 3 Due

Start thinking about Project 4

21

4/14/14

Cell Spreading and Cell Fate

1) Folkman, "Influence of Geometry on Control of Cell Growth"
2) Chen, et al., “Geometric Control of Cell Life and Death”\

Discuss Project 4 Topics

22

4/17/14

Spreading and Stiffness in Differentiation

1. Matrix Elasticity Directs Stem Cell Lineage Specification
2. Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment

4/21/14

23

4/23/14

2D is not 3D

Olin Monday (Wednesday)

1) Taking Cell-Matrix Adhesions to the Third Dimension
2) Alisha's adhesion table
3)[good review article to read, optional] Peyton, "The emergence of ECM mechanics and cytoskeletal tension as important regulators of cell function"

24

4/24/14

Stiffness and tumors

1) [OPTIONAL REVIEW for BACKGROUND] A tense situation: forcing tumour progression
2) Tensional homeostasis and the malignant phenotype

Project 4 Drafts Due

25

4/28/14

1) Computational Model for Cell Migration in Three-Dimensional Matrices
2) Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis

26

5/1/14

TBD

Project 4 Due

TBA

Final Presentations