Lecture 2: Cellular Microenvironment & ECM
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Questions and Answers

PLCγ, phospholipase Cγ, is listed as a potential sensor in various cells.

False (B)

Piezo1 and Piezo2 are part of a newly identified family of mechanosensitive cation channels.

True (A)

Fluid shear stress does not activate any proteins that sense the cellular microenvironment.

False (B)

Arachidonic acid is referred to as AA in the context of cellular sensors.

<p>True (A)</p> Signup and view all the answers

Degenerin, often abbreviated as Deg, is a type of ion channel.

<p>False (B)</p> Signup and view all the answers

Transient receptor potential is abbreviated as TRP and is involved in cellular microenvironment sensing.

<p>True (A)</p> Signup and view all the answers

Adenylyl cyclase, abbreviated as AC, is not implicated in the response to membrane stretch.

<p>False (B)</p> Signup and view all the answers

The epithelial sodium channel is referred to as ENaC and is involved in mechanosensation.

<p>True (A)</p> Signup and view all the answers

Epithelial and endothelial cells adhere to the basement membrane via multiple surfaces.

<p>False (B)</p> Signup and view all the answers

Mesenchymal cells, such as fibroblasts, are surrounded by the extracellular matrix.

<p>True (A)</p> Signup and view all the answers

Hyaluronic acid is considered a proteoglycan as it has a specific protein core.

<p>False (B)</p> Signup and view all the answers

The three main families of proteoglycans include modular proteoglycans and long-chain proteoglycans.

<p>False (B)</p> Signup and view all the answers

Proteoglycans are hydrophobic molecules that adopt compact conformations.

<p>False (B)</p> Signup and view all the answers

Genetic diseases can be linked to mutations in proteoglycan genes.

<p>True (A)</p> Signup and view all the answers

SLRPs are not involved in any signaling pathways.

<p>False (B)</p> Signup and view all the answers

TGFb activation is unrelated to proteoglycans in inflammatory responses.

<p>False (B)</p> Signup and view all the answers

FRET-labeled fibronectin should comprise more than 10% to ensure effective intermolecular energy transfer.

<p>False (B)</p> Signup and view all the answers

Basement membrane modular PGs have only anti-angiogenic functions.

<p>False (B)</p> Signup and view all the answers

The human degradome includes exactly 500 proteases distributed intra- and extracellularly.

<p>False (B)</p> Signup and view all the answers

Syndecans and glypicans are types of collagen found in the extracellular matrix.

<p>False (B)</p> Signup and view all the answers

There are more than 28 types of elastin identified in vertebrates.

<p>False (B)</p> Signup and view all the answers

Cysteine proteases are one of the five families of proteases in the human degradome.

<p>True (A)</p> Signup and view all the answers

Fibronectin is exclusively derived from synthetic sources for use in cell media.

<p>False (B)</p> Signup and view all the answers

Fibronectin assembly into longer fibrils is facilitated by cell-surface binding of the soluble FN dimer.

<p>True (A)</p> Signup and view all the answers

Elastin provides recoil to tissues that are not subject to repeated stretch.

<p>False (B)</p> Signup and view all the answers

All proteases consist of a signal sequence, a propeptide, and a catalytic domain.

<p>True (A)</p> Signup and view all the answers

Aspartic acid proteases are not classified within the human degradome's protease families.

<p>False (B)</p> Signup and view all the answers

Interstitial matrices and pericellular matrices are the only classifications of extracellular matrices.

<p>True (A)</p> Signup and view all the answers

Fibronectin can be harvested and integrated into the extracellular matrix by cells.

<p>True (A)</p> Signup and view all the answers

The majority of collagen molecules form single-stranded helical structures.

<p>False (B)</p> Signup and view all the answers

Threonine proteases are the dominant type of proteases in the human degradome.

<p>False (B)</p> Signup and view all the answers

Integrin clustering can promote fibronectin-fibril assembly by exposing cryptic binding sites.

<p>True (A)</p> Signup and view all the answers

Aged vascular smooth muscle cells (VSMCs) contribute to chronic low-grade inflammation in the aortic wall.

<p>False (B)</p> Signup and view all the answers

Excessive deposition of collagen in the aged aortic wall is a result of adventitial fibroblasts.

<p>True (A)</p> Signup and view all the answers

Elastin fragmentation in the intima is a characteristic of a youthful aortic wall.

<p>False (B)</p> Signup and view all the answers

Collagen fibers in the adventitia serve to enhance the elasticity of the aortic wall.

<p>False (B)</p> Signup and view all the answers

Tumorigenesis and progression are driven by stromal deregulation in the aged microenvironment.

<p>True (A)</p> Signup and view all the answers

In linear elastic materials, stress is related to strain by the equation $σ = E(ε)$ without loss of mechanical energy.

<p>True (A)</p> Signup and view all the answers

Nonlinear elastic materials exhibit a stress-strain relationship where stress is directly proportional to strain.

<p>False (B)</p> Signup and view all the answers

Viscoelastic materials can both store elastic energy and lose mechanical energy during deformation.

<p>True (A)</p> Signup and view all the answers

Poroelastic materials respond to deformation by exhibiting a time-independent mechanical response.

<p>False (B)</p> Signup and view all the answers

Mechanical plasticity refers to irreversible deformation of a material after mechanical loading.

<p>True (A)</p> Signup and view all the answers

Biological tissues primarily exhibit linear elastic behavior in their mechanical properties.

<p>False (B)</p> Signup and view all the answers

The hysteresis observed in viscoelastic materials during loading and unloading indicates a loss of energy.

<p>True (A)</p> Signup and view all the answers

Stress relaxation occurs when a material exhibits a constant deformation and its stress decreases over time.

<p>True (A)</p> Signup and view all the answers

Flashcards

Cellular Microenvironment

The immediate surroundings of a cell, encompassing all the components and factors that influence its behavior and function.

Extracellular Matrix (ECM)

A complex mixture of molecules that provides structural support, mediates cell-cell interactions, and influences cell behavior.

Mechanosensors

Proteins that sense and respond to changes in the cellular microenvironment, especially mechanical forces like stretching or pressure.

Piezo Proteins (Piezo1 and Piezo2)

A family of proteins responsible for detecting and responding to mechanical stimuli in the cell's environment.

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Transient Receptor Potential (TRP) Channels

A family of ion channels that are activated by mechanical changes in the cell membrane, allowing ions to flow in and out.

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TREK-1 Channel

A type of potassium channel that is activated by stretching or mechanical stress.

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Degenerins

A class of proteins found in sensory cells that respond to mechanical stimuli, potentially involved in sensing touch and pressure.

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Epithelial Sodium Channel (ENaC)

A type of ion channel that is activated by mechanical forces in the cell membrane, allowing sodium ions to flow across.

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What are Proteoglycans?

Proteoglycans are complex molecules made of long chains of sugars called glycosaminoglycans (GAGs) attached to a protein core. They are essential for forming the extracellular matrix (ECM) which is the supportive network of cells.

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What are the main families of Proteoglycans?

The three main families of proteoglycans are small leucine-rich proteoglycans (SLRPs), modular proteoglycans, and cell-surface proteoglycans.

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What are Glycosaminoglycans (GAGs)?

Glycosaminoglycans are long chains of sugars found in proteoglycans. They attract water, making the ECM gel-like.

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What is Hyaluronic Acid?

Hyaluronic acid is a unique type of GAG that is not attached to a protein core. It is important for the ECM's gel-like structure.

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What are Small Leucine-Rich Proteoglycans (SLRPs)?

SLRPs are a type of proteoglycan involved in many signaling pathways, like activating growth factor receptors and regulating inflammation.

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What is the role of the Extracellular Matrix (ECM)?

The ECM provides structural support for cells, helps cells communicate, and plays a role in tissue repair and development.

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How do cells interact with the ECM?

Mesenchymal cells, like fibroblasts, are completely surrounded by the ECM, while epithelial and endothelial cells only adhere to the basement membrane on one side.

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Why are Proteoglycan gene mutations important?

Mutations in genes for proteoglycans can lead to various genetic diseases. This is due to their critical role in tissue structure and function.

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FRET-labeled FN as a mechanical strain sensor

A type of sensor that utilizes Förster resonance energy transfer (FRET) to detect changes in the physical properties of the extracellular matrix (ECM).

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FRET-labeling in FN

FN, a protein found in the ECM, can be modified by attaching a fluorophore (FRET-labeled) to its cryptic cysteines.

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FRET-labeling

The process of tagging a protein with a fluorophore (FRET-labeled).

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Proteases

A group of enzymes that break down proteins.

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Degradome

A collection of all proteases within an organism, including those involved in breaking down proteins in the ECM.

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Metalloproteases

A specific family of proteases that are characterized by a zinc atom in their active site.

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Serine proteases

A specific family of proteases that are characterized by a serine residue in their active site.

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Cysteine proteases

A specific family of proteases that are characterized by a cysteine residue in their active site.

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Adventitia in the aorta

The outermost layer of the aorta, containing collagen fibers that help prevent overexpansion and various cellular and non-cellular components that maintain the overall health of the aortic wall.

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Vascular Smooth Muscle Cells (VSMCs)

Specialized cells in the blood vessel walls responsible for contracting and relaxing to regulate blood pressure and flow.

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Cellular Senescence

The process of aging in cells, leading to a loss of normal function and an increased risk of diseases.

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Microenvironment

The environment surrounding cells, including ECM, other cells, and signaling molecules, that can influence cell behavior and health.

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What are modular PGs?

Modular PGs are a type of proteoglycans that can influence cell adhesion, migration, and proliferation. They can be found in the basement membrane and on cell surfaces.

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What are some basement membrane modular PGs?

Perlecan, agrin, and collagen type XVIII are examples of modular PGs found in the basement membrane. These PGs play a dual role by promoting and inhibiting blood vessel formation.

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What are some cell-surface modular PGs?

Syndecans and glypicans are modular PGs found on cell surfaces. They act as co-receptors, helping signaling receptors bind to their ligands.

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What are the main fibrous proteins in the ECM?

Collagens, elastins, fibronectins, and laminins are major fibrous proteins found in the ECM. They provide structural support and contribute to tissue function.

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Describe the structure of collagen molecules.

Collagen molecules are typically arranged in a triple helix structure. This structure allows them to form different supramolecular assemblies, such as fibrils and networks.

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What are the two main types of collagen assemblies?

Fibrous collagens are responsible for forming the backbone of collagen fibril bundles in the interstitial tissue stroma, whereas network collagens are incorporated into the basement membrane.

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How does fibronectin assemble into fibrils?

Fibronectin is a soluble dimer that binds to cell surfaces and assembles into longer fibrils. This process is facilitated by cell contraction and integrin clustering.

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What is tenascin and how does it influence cell behavior?

Tenascin is another ECM protein, similar to fibronectin, that influences cell behavior, such as promoting fibroblast migration during wound healing.

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Linear Elastic Material

A type of material where stress and strain are linearly related for small strains, making it behave elastically and reversibly, with no loss of energy.

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Nonlinear Elastic Material

A material where stress and strain do not have a linear relationship, even for small strains. Deformation is not always reversible.

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Viscoelastic Material

A material that combines both elastic (spring-like) and viscous (fluid-like) properties. Stores energy like a solid and loses energy like a fluid, showing hysteresis in the stress-strain relationship.

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Poroelastic Material

A type of material experiencing a time-dependent response to applied load due to water flow in or out of a porous structure. Deformation triggers volume changes.

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Plastic Material

A material that deforms irreversibly after a load is applied. It will not return to its original shape.

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Elastic Material

A material that returns to its original shape after a load is removed. The stress-strain relationship follows the same path during loading and unloading.

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Stress Relaxation

A material that experiences a delayed response to a constant force. The stress decreases over time.

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Creep

A material that exhibits increased deformation or strain over time when subjected to a constant stress.

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Study Notes

Lecture 2: Cellular Microenvironment & Extracellular Matrix

  • This lecture covers the cellular microenvironment, matrix components, 3D organization of matrix components, and the physicochemical properties of the matrix and aging.

Cellular Microenvironment

  • Neighboring cells, tissue-specific cells (e.g., nerve cells, stem cells), and the extracellular matrix influence cellular microenvironments.
  • Cellular components include soluble factors (e.g., growth factors, cytokines), cytoskeletal elements, cytoplasmic mediators, nuclear mediators, and cell-cell contact molecules (e.g., cadherins).
  • There are interactions between the cell and signaling factors via binding, stress, strain (mechanical), and physical fields (electrical, thermal, etc.).

Extracellular Matrix (ECM) Components

  • Proteoglycans (PGs) are composed of glycosaminoglycan (GAG) chains attached to a protein core. Different families exist (small leucine-rich proteoglycans (SLRPs), modular proteoglycans, and cell-surface proteoglycans).
  • PGs are hydrophilic, forming highly extended structures for hydrogel formation.
  • Important matrix components include collagens (types I, III, etc.), elastins, fibronectins, and laminins, many of varied types.
  • Fibrous collagens form the backbone of fibril bundles, with network collagens found in basal membranes.
  • Elastin fibers provide recoil to tissues.
  • Fibronectin (FN) dimer is critical for fibril assembly and linked to cell contraction.
  • Mechanical properties of ECM link to mechanical responses in cells (cell mechanotransduction).

3D Organization of Matrix Components

  • 3D organization of the ECM (extracellular matrix) is crucial for different tissue types, involving ECM components (proteoglycans and various proteins) in their spatial organization and assembly.
  • The mechanical/physical properties of the matrix contribute to the spatial assembly of the ECM.

Physicochemical Properties of the Matrix and Aging

  • The physical properties of the ECM (e.g., stiffness, elasticity, and porosity) are critical in cellular behavior (cell-type specific mechanisms).
  • Matrix properties influence cell behavior including cell adhesion, migration, and proliferation, and are vital for the appropriate interactions within the ECM.
  • Ageing leads to alterations in the ECM, impacting its stiffness, structure, and function. This has implications for cellular functions and responses in the aging organism.

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Description

This quiz dives into the concepts of cellular microenvironments and the extracellular matrix (ECM). It discusses the structure, components, and influences of the ECM on cellular behavior and the physical interactions that occur within this microenvironment. Test your understanding of proteoglycans, signaling factors, and the overall organization of matrix components.

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