Microtubules and Focal Adhesions Quiz

Lecture 2: Cellular Microenvironment & Extracellular Matrix

• Cellular microenvironment is a key focus.
• Matrix components are crucial.
• The 3D organization of matrix components is examined.
• Physicochemical properties of the matrix and their relationship to aging are discussed.

Lecture 3: Cell Morphometric Changes & Cytoskeletal Remodeling

• Cytoskeletal components and their cross-talk regulate cell morphology.
• The extracellular matrix (ECM) dictates the 3D organization of cytoskeletal components.
• Cytoskeletal control of nuclear morphology is studied.
• Cell morphometric and cytoskeletal alterations in aging are explored.

Cytoskeletal Components and Cell Morphology

• Actin, microtubules, and intermediate filaments are key cytoskeletal components.
• These components play critical roles in cell morphology and function.
• The cytoskeleton is a complex network of proteins that provides structural support, facilitates intracellular transport, and enables cell movement.

Cytoskeletal Components (Detailed)

• Actin filaments are involved in polymerization and depolymerization.
• Microtubules are composed of alpha and beta-tubulin dimers.
• Intermediate filaments are composed of various protein subunits.
• The cytoskeleton plays multiple cellular roles, including mechanical strength, intracellular transport, and spatial organization.

Cross-talk Between Actin and Microtubule Cytoskeletons

• Microtubules can be guided by actin bundles.
• Microtubule anchoring and stabilization from actin.
• Actin acts as a physical barrier during microtubule growth.
• Actin nucleation factors may initiate actin filament creation at microtubule ends.
• Mechanical interaction occurs between microtubules and actin during membrane protrusions.

Shared Regulators of Actin and Microtubule Dynamics

• Rho family GTPases are shared regulators of actin and microtubule dynamics.
• Rho GTPases interact with actin- and microtubule-associated proteins.
• Microtubules can influence Rho GTPase activity locally.

Cross-talk Between Actin and Microtubule Cytoskeleton at Focal Adhesions

• Focal adhesions link the extracellular matrix to the actin cytoskeleton.
• Integrins are critical for cell adhesion.
• Recycling and new delivery of integrins depend on microtubule transport mechanisms.
• Microtubule guidance and stabilization, along with signaling complex formation at microtubule ends, impact focal adhesions.
• Micro-tubules are captured at focal adhesion-associated sites via CLASP family members and related proteins.

Cell-Matrix and Cell-Cell Sensing: Common Mechanisms

• Mechanical forces generated by actomyosin interactions are resisted by ECM and cell-cell adhesions.
• This creates a tensional prestress in cells and tissues.
• Actomyosin interactions, ECM, and cell-cell adhesions are crucial for structure and function.

Cell Adhesion to the Matrix Shapes the Cell Nucleus

• Nascent adhesions form at the leading edge of cell protrusions.
• These adhesions involve multiple ligand-bonded integrins and related proteins.
• Adhesome proteins, including vinculin, are recruited for tension- and/or tension-independent processes.
• The actin network interacts with proteins controlling adhesion to convert forces.

Extracellular Matrix Control of Nuclear Morphology and Position

• Mechanical stimulation from the ECM influences cytoskeletal network organization.
• Force transmission alters cytoskeletal network organization via integrins.
• Nesprins and SUN domain proteins integrate cell-matrix forces with nuclear organization.
• The nuclear lamina is crucial for force transmission to the nucleus, influencing gene expression.

Summary of Links Between Inner Nuclear Membrane and Cytoskeleton Interactions

• Diverse factors connect the inner nuclear membrane to the cytoskeleton.
• Kinesin-1, dynein, and other proteins bridge these components.
• Interaction sites exist at microtubules and intermediate fibers for cell cycle progression and other cellular processes.

Experiments to Demonstrate Prestressed Nuclear Architecture in Living Cells

• Experiments demonstrate nuclear architecture impacts force balance in living cells.
• Force balance changes can be studied with different cytoskeletal factors.
• This research focuses on how isolated nuclei respond to force.

Cytoskeleton Organization is Dependent on Cell Microenvironment Interaction

• Cytoskeleton organization shifts in response to varying microenvironments.
• Cell adhesion dynamics are crucial.
• Focal Adhesions, stabilization, and nascent adhesions influence the cytoskeleton.

Fragmentation of Collagen Fibrils within Aged/Photoaged Skin Causes Collapse of Fibroblasts

• Collagen fragmentation correlates with aged skin fibroblast collapse.
• Mechanical tension is crucial for fibroblast health and dermal structure.
• Loss of structure can affect collagen synthesis and fibroblast response.

The Proposed Model for RhoA/Sun2-Mediated Increase of Cytoskeletal Stiffness in Progeria Cells

• The ECM, cytoskeleton, and nucleoskeleton are connected.
• Increased ECM stiffness correlates with RhoA activation and cytoskeleton stiffness.
• RhoA activation correlates with ROS production, inflammation, and DNA damage.

Cellular Senescence is Associated with Reorganization of the Microtubule Cytoskeleton

• HDAC6, Rock1, and γ-tubulin depletion impacts senescent cells.
• Senescent cells show microtubule stabilization, and impaired cell migration.

Imbalanced Nucleo-Cytoskeletal Connections

• Imbalanced nucleo-cytoskeletal connections lead to polarity defects in progeria and aging.
• Nesprin-2G, SUN1, and SUN2 interact with microtubules to affect cell signaling and shape.

Biological Age-Dependent Changes of Cell Morphology

• Cellular morphology alters with age.
• Cell size, shape, and cellular traction force change between young and older cells.

Age-Dependent Alteration of Nuclear Morphology

• Nucleus size and shape change with age in fibroblasts.
• Nucleus area, parameters and aspects are different between young and old cells.

Age-Dependent Alteration of Cell Motility

• Cell motility declines with age and is linked to functional and molecular alterations.
• Cell trajectories and total cell distance correlate with age and cell type.

Heterogeneity in Cellular Mechanical Responses with Aging

• Cellular response and aging have functional heterogeneity.
• Biophysical parameters vary in a group of cells according to chronological age.

Heterogeneity in Cellular Functional Responses with Aging

• Cellular responses display variability with age in physiological processes.
• Diverse molecular responses, including ATP production, influence age-related changes.

Mechanobiological Changes in Aging

• Cellular response to mechanical stress changes with aging.
• ECM, cytoskeleton, and cell mechanics all change in function with age.
• These changes include ECM crosslinking and stiffness, actin polymerization, and cell mechanics.

Lecture 4: Proteostasis

• Proteostasis maintains cellular protein homeostasis efficiently in cells.
• This includes the folding, refolding, and degradation of proteins in cells.
• Cellular processes such as protein homeostasis, folding and degradation are altered by aging and stressors.

Test your knowledge on the interaction between microtubules and focal adhesions. This quiz covers key proteins involved in cellular dynamics, the role of Rho GTPases, and the importance of the cytoskeleton in cell motility. Dive deep into the mechanisms that regulate these complex processes.