Master’s-Level Cell Biology & Advanced Molecular Biology Notes

1. Definition

Mechanotransduction is the process by which cells sense mechanical forces and convert them into biochemical signals and cellular responses.

Mechanical stimuli include:

• Stretch
• Compression
• Shear stress
• Matrix stiffness
• Cell–cell tension
• Cell–matrix tension
• Membrane deformation
• Fluid flow

The basic principle is:

MECHANICAL FORCE
       ↓
MECHANOSENSOR
       ↓
CONFORMATIONAL / STRUCTURAL CHANGE
       ↓
BIOCHEMICAL SIGNAL
       ↓
SIGNALING CASCADE
       ↓
GENE EXPRESSION
       ↓
CELLULAR RESPONSE

---

2. Why Mechanotransduction Is Important

Mechanotransduction allows cells to respond to their physical environment.

It regulates:

• Cell shape
• Cell migration
• Cell adhesion
• Cell proliferation
• Differentiation
• Survival
• Tissue development
• Stem-cell fate
• Vascular function
• Bone remodeling
• Muscle function
• Wound healing

Thus, the cell is not responding only to chemical signals.

Cells continuously integrate biochemical and mechanical information.

---

3. Sources of Mechanical Forces

Mechanical forces can originate from either the external environment or neighboring cells.

                 MECHANICAL INPUTS
                        │
       ┌────────────────┼────────────────┐
       ↓                ↓                ↓
  ECM stiffness     Fluid flow       Cell-cell
                                      tension
       │                │                │
       └────────────────┼────────────────┘
                        ↓
                MECHANOSENSING
                        ↓
                CELLULAR RESPONSE

---

4. Major Mechanosensors

Important cellular mechanosensors include:

1. Integrins

Sense extracellular matrix forces.

2. Mechanosensitive ion channels

Examples:

• Piezo1
• Piezo2

3. Cadherins

Sense forces transmitted between neighboring cells.

4. Cytoskeleton

Actin, microtubules and intermediate filaments transmit mechanical forces.

5. Nuclear envelope

The nucleus itself can sense mechanical stress.

6. Primary cilia

Can detect mechanical stimuli, particularly fluid flow.

---

5. Integrin-Mediated Mechanotransduction

Integrins are transmembrane receptors that connect the:

Extracellular matrix → cytoskeleton

             EXTRACELLULAR MATRIX
════════════════════════════════════
                  │
               INTEGRIN
                  │
                  │
                TALIN
                  │
               VINCULIN
                  │
                  ↓
        ACTIN CYTOSKELETON
════════════════════════════════════

This arrangement allows mechanical forces to pass between the ECM and intracellular cytoskeleton.

---

6. Focal Adhesions

Focal adhesions are major mechanotransduction platforms.

They contain:

• Integrins
• Talin
• Vinculin
• Kindlin
• Paxillin
• FAK
• Src
• Actin filaments

             ECM
════════════════════════
             │
          INTEGRIN
             │
           TALIN
             │
         VINCULIN
             │
       PAXILLIN / FAK
             │
             ↓
       ACTIN FILAMENT
════════════════════════

They function as both adhesion structures and signaling centers.

---

7. Force-Induced Talin Activation

Talin is particularly important in mechanotransduction.

Mechanical force can alter talin conformation and expose binding sites for other proteins.

Mechanical force
       ↓
Integrin
       ↓
Talin tension
       ↓
Talin conformational change
       ↓
Vinculin recruitment
       ↓
Focal adhesion maturation
       ↓
Stronger adhesion

This represents a classic mechanochemical feedback loop.

---

8. Focal Adhesion Kinase

FAK is an important signaling protein associated with focal adhesions.

Mechanical stimulation can promote:

Integrin engagement
       ↓
FAK activation
       ↓
Src signaling
       ↓
MAPK / PI3K pathways
       ↓
Cell survival / proliferation / migration

Thus, mechanical information can ultimately alter gene expression.

---

9. Mechanosensitive Ion Channels

Mechanosensitive ion channels convert membrane deformation into electrical and biochemical signals.

One of the most important families is the Piezo family.

Mechanical force
       ↓
Membrane deformation
       ↓
PIEZO CHANNEL
       ↓
Ion influx
       ↓
Ca²⁺ signaling
       ↓
Cellular response

---

10. Piezo1

Piezo1 is a major mechanosensitive ion channel.

It responds to mechanical forces such as:

• Membrane tension
• Stretch
• Shear-related forces

Opening of the channel allows cations, including Ca²⁺, to enter the cell.

Mechanical stimulus
        ↓
     Piezo1
        ↓
     Ca²⁺ influx
        ↓
Ca²⁺-dependent signaling
        ↓
Cellular response

---

11. Piezo2

Piezo2 has a particularly important role in mechanosensation in the nervous system.

It contributes to the detection of:

• Touch
• Pressure
• Mechanical deformation

Therefore, Piezo channels connect physical forces to electrical and biochemical signaling.

---

12. Calcium as a Mechanotransduction Signal

Ca²⁺ is one of the most important second messengers generated by mechanical stimulation.

Mechanical force
       ↓
Mechanosensitive channel
       ↓
Ca²⁺ influx
       ↓
Calmodulin / CaMK
       ↓
Kinases / transcriptional pathways
       ↓
Gene expression

Ca²⁺ can influence:

• Cytoskeletal organization
• Muscle contraction
• Gene expression
• Cell migration
• Secretion
• Metabolism

---

13. Cadherin-Mediated Mechanotransduction

Cadherins mediate cell–cell adhesion.

In epithelial cells, mechanical force can be transmitted through:

Cadherin → catenin → actin

Cell A                       Cell B

Actin ════                  ════ Actin
       │                       │
    Catenin                 Catenin
       │                       │
    Cadherin ═════════════ Cadherin
              ↑
           Force

Important proteins include:

• E-cadherin
• α-catenin
• β-catenin

---

14. α-Catenin as a Mechanosensor

α-catenin links cadherin-associated complexes to actin.

Mechanical tension can alter its conformation and expose binding sites for proteins such as vinculin.

Tension
   ↓
α-catenin conformational change
   ↓
Vinculin recruitment
   ↓
Stronger actin linkage
   ↓
Junction reinforcement

This is another example of force-dependent protein conformational change.

---

15. Cytoskeleton as a Mechanotransduction System

The cytoskeleton is not simply a structural scaffold.

It can:

• Transmit force
• Generate force
• Sense force
• Redistribute force
• Activate signaling pathways

MECHANICAL FORCE
       ↓
MEMBRANE
       ↓
ADHESION COMPLEX
       ↓
ACTIN
       ↓
CYTOSKELETAL NETWORK
       ↓
NUCLEUS
       ↓
GENE REGULATION

---

16. Actomyosin Contractility

The actin–myosin system is a major generator of intracellular mechanical force.

Actin filament
════════════════════
      ↑
    Myosin II
      ↓
════════════════════
Actin filament

        ↓
  CONTRACTILE FORCE

RhoA–ROCK signaling increases myosin II-dependent contractility.

RhoA
 ↓
ROCK
 ↓
Myosin regulation
 ↓
Actomyosin contraction
 ↓
Mechanical tension

---

17. RhoA–ROCK Pathway

A simplified mechanism:

Mechanical stimulation
        ↓
      RhoA
        ↓
      ROCK
        ↓
Myosin light-chain regulation
        ↓
Myosin II activation
        ↓
Actomyosin contractility
        ↓
Increased cellular tension

This can strengthen focal adhesions and cell–cell junctions.

---

18. Mechanical Feedback

An important principle is that force can generate more force.

Mechanical force
      ↓
Integrin activation
      ↓
Actin tension
      ↓
Talin unfolding
      ↓
Vinculin recruitment
      ↓
Focal adhesion maturation
      ↓
Greater force transmission

This is a positive-feedback mechanism.

---

19. ECM Stiffness

Cells can sense the mechanical stiffness of their extracellular matrix.

Two environments:

SOFT ECM

~~~~~~~~~~~~~~
      ↓
Low resistance
      ↓
Low contractility


STIFF ECM

══════════════
      ↓
High resistance
      ↓
High contractility

Cells generally generate greater cytoskeletal tension when interacting with a mechanically stiff substrate.

---

20. Matrix Stiffness and Cell Fate

ECM stiffness can influence:

• Cell proliferation
• Migration
• Differentiation
• Stem-cell fate

Therefore:

Mechanical properties of the extracellular matrix can act as biological information.

---

21. YAP/TAZ Pathway

One of the most important modern mechanotransduction pathways involves:

YAP and TAZ

These are transcriptional coactivators regulated by the Hippo pathway and mechanical state.

Mechanical environment
        ↓
Cytoskeletal tension
        ↓
Hippo pathway regulation
        ↓
YAP / TAZ localization
        ↓
Nucleus
        ↓
Gene transcription

---

22. YAP/TAZ Nuclear Localization

A simplified model:

Soft environment

Soft ECM
   ↓
Low cytoskeletal tension
   ↓
YAP/TAZ excluded from nucleus
   ↓
Reduced transcription of target genes

Stiff environment

Stiff ECM
   ↓
High cytoskeletal tension
   ↓
YAP/TAZ nuclear localization
   ↓
Transcriptional activation

This is an important concept in tissue biology and cancer biology.

---

23. YAP/TAZ and TEAD

YAP and TAZ regulate transcription largely through interaction with transcription factors of the TEAD family.

Mechanical force
       ↓
YAP / TAZ
       ↓
Nucleus
       ↓
TEAD
       ↓
Target genes
       ↓
Growth / survival / differentiation

---

24. Mechanotransduction and Gene Expression

Mechanical signals can reach the nucleus through several pathways.

Mechanical force
       ↓
Integrin / cadherin / channel
       ↓
Cytoskeleton
       ↓
Nuclear envelope
       ↓
Transcription factors
       ↓
Chromatin
       ↓
Gene expression

Thus, mechanical stimuli can produce long-term changes in cell phenotype.

---

25. LINC Complex

The LINC complex connects the cytoskeleton to the nucleus.

LINC stands for:

Linker of Nucleoskeleton and Cytoskeleton

Major components include:

• SUN proteins
• KASH proteins

CYTOSKELETON
     │
     ↓
 KASH proteins
     │
════════════════
Nuclear envelope
════════════════
     │
 SUN proteins
     │
     ↓
NUCLEAR LAMINA
     │
     ↓
CHROMATIN

---

26. Mechanical Force and the Nucleus

The nucleus is mechanically responsive.

Force transmitted through the cytoskeleton can deform:

• Nuclear envelope
• Nuclear lamina
• Chromatin

This can influence:

• Nuclear shape
• Chromatin organization
• Transcription
• DNA damage responses

---

27. Lamin Proteins

Nuclear lamins form the nuclear lamina.

They provide:

• Nuclear mechanical stability
• Structural support
• Regulation of nuclear organization

Cytoskeletal force
       ↓
LINC complex
       ↓
Nuclear lamina
       ↓
Nuclear deformation
       ↓
Chromatin response

---

28. Mechanotransduction and Chromatin

Mechanical forces can alter chromatin organization.

Possible sequence:

Mechanical force
       ↓
Nuclear deformation
       ↓
Chromatin reorganization
       ↓
Altered transcription factor accessibility
       ↓
Gene expression

Therefore, mechanotransduction can extend all the way from the extracellular matrix to the genome.

---

29. Shear Stress

Shear stress is particularly important in vascular endothelial cells.

Blood flow generates mechanical forces along the endothelial surface.

BLOOD FLOW
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

─────────────────────────────
ENDOTHELIAL CELL
─────────────────────────────

Endothelial cells detect flow through multiple mechanosensory systems.

---

30. Endothelial Mechanotransduction

Important mechanosensory components include:

• Integrins
• Cell–cell junctions
• Mechanosensitive channels
• Primary cilia
• Glycocalyx
• Cytoskeleton

Mechanical signaling influences:

• Nitric oxide production
• Vascular tone
• Inflammation
• Endothelial alignment
• Gene expression

---

31. Mechanotransduction in Bone

Bone is a classic mechanosensitive tissue.

Mechanical loading is detected by cells including:

• Osteocytes
• Osteoblasts

Mechanical loading
       ↓
Bone deformation
       ↓
Osteocyte mechanosensing
       ↓
Ca²⁺ / signaling pathways
       ↓
Bone remodeling

This allows bone to adapt to mechanical demands.

---

32. Mechanotransduction in Muscle

Muscle cells experience substantial mechanical forces.

Mechanotransduction regulates:

• Growth
• Adaptation
• Protein synthesis
• Cytoskeletal organization

Mechanical load
      ↓
Integrin / cytoskeleton
      ↓
Signaling
      ↓
Gene expression
      ↓
Muscle adaptation

---

33. Mechanotransduction in Stem Cells

Mechanical properties of the microenvironment influence stem-cell behavior.

Mechanical environment
        ↓
Cytoskeletal tension
        ↓
YAP/TAZ
        ↓
Gene expression
        ↓
Stem-cell fate

This is particularly important in tissue engineering and regenerative medicine.

---

34. Mechanotransduction and Development

During development, cells experience:

• Tissue tension
• Compression
• Cell migration
• Cell crowding
• ECM stiffness

Mechanotransduction helps coordinate:

• Morphogenesis
• Organ development
• Tissue patterning
• Cell differentiation

---

35. Mechanotransduction in Wound Healing

During wound repair:

Tissue injury
     ↓
Changes in mechanical environment
     ↓
Cell migration
     ↓
Actomyosin remodeling
     ↓
ECM remodeling
     ↓
Tissue closure

Mechanical forces interact with growth-factor signaling during the repair process.

---

36. Mechanotransduction and Cancer

Tumors frequently develop altered mechanical environments.

These can include:

• Increased ECM stiffness
• Elevated tissue tension
• Abnormal cell–cell forces
• Altered cytoskeletal contractility

ECM stiffening
      ↓
Integrin signaling
      ↓
Cytoskeletal tension
      ↓
YAP/TAZ activation
      ↓
Proliferation / survival
      ↓
Tumor progression

Mechanotransduction is therefore an important area of cancer biology.

---

37. Mechanotransduction and Fibrosis

Fibrosis is associated with excessive ECM deposition and tissue stiffening.

A potential feedback loop is:

ECM deposition
      ↓
Increased stiffness
      ↓
Mechanotransduction
      ↓
Fibroblast activation
      ↓
More ECM production
      ↓
Further stiffening

This creates a positive-feedback loop.

---

38. Mechanotransduction and Cell Migration

Mechanical cues can determine migration direction.

Mechanical cue
      ↓
Polarization
      ↓
Rac activation at leading edge
      ↓
Actin polymerization
      ↓
Adhesion
      ↓
RhoA-dependent contraction
      ↓
Migration

Thus mechanotransduction is closely connected to cell polarity.

---

39. Mechanotransduction and Calcium Signaling

A major pathway is:

Force
 ↓
Piezo channel
 ↓
Ca²⁺ influx
 ↓
Calmodulin
 ↓
CaMK / other effectors
 ↓
Cytoskeletal remodeling
 ↓
Gene regulation

Calcium can therefore act as a bridge between mechanical stimulation and intracellular signaling.

---

40. Mechanotransduction and Membrane Tension

The plasma membrane itself can respond to tension.

Increased membrane tension can:

• Activate mechanosensitive channels
• Alter membrane curvature
• Influence endocytosis
• Affect exocytosis
• Change membrane–cytoskeleton interactions

Mechanical stretch
       ↓
Membrane tension
       ↓
Channel / trafficking response
       ↓
Cell adaptation

---

41. Mechanotransduction and Cell Volume

Mechanical forces can influence:

• Cell volume
• Osmotic balance
• Ion transport
• Cytoskeletal organization

Mechanosensitive channels can participate in adaptive responses to changes in membrane tension and cellular mechanics.

---

42. Mechanotransduction Is Multiscale

Mechanotransduction operates at multiple levels:

EXTRACELLULAR
     ↓
ECM
     ↓
Integrins / cadherins
     ↓
CYTOSKELETON
     ↓
Nuclear envelope
     ↓
CHROMATIN
     ↓
GENOME

The response can therefore range from milliseconds to hours or days, depending on the mechanism.

---

43. Fast vs Slow Mechanotransduction

Fast response

Usually involves:

• Ion channels
• Ca²⁺ influx
• Cytoskeletal changes

Force → channel → Ca²⁺

Slow response

Usually involves:

• Transcription factors
• Chromatin
• Gene expression
• Differentiation

Force → signaling → nucleus → transcription

---

44. Biochemical vs Mechanical Signaling

Feature	Biochemical signaling	Mechanotransduction
Stimulus	Ligand	Force
Sensor	Receptor	Mechanosensor
Signal	Second messenger	Mechanical + biochemical
Major systems	GPCR/RTK etc.	Integrin/Piezo/cadherin
Cytoskeleton	Often downstream	Often central
Output	Gene expression/function	Gene expression/function

In reality, the two systems are extensively interconnected.

---

45. Integrated Mechanotransduction Pathway

                    MECHANICAL FORCE
                           │
          ┌────────────────┼─────────────────┐
          ↓                ↓                 ↓
       INTEGRIN         CADHERIN          PIEZO
          │                │                 │
          ↓                ↓                 ↓
       TALIN          α-CATENIN           Ca²⁺
          │                │                 │
       VINCULIN        VINCULIN             │
          │                │                 │
          └──────────┬─────┴─────────────────┘
                     ↓
              ACTIN CYTOSKELETON
                     │
                RhoA / ROCK
                     │
              MYOSIN II FORCE
                     │
                     ↓
              NUCLEAR COUPLING
                     │
                 LINC COMPLEX
                     │
                     ↓
                  NUCLEUS
                     │
                  YAP / TAZ
                     │
                     ↓
              GENE EXPRESSION
                     │
                     ↓
              CELLULAR RESPONSE

---

46. Mechanotransduction and Feedback

Mechanotransduction frequently operates through feedback loops.

Example: ECM stiffness

Stiff ECM
   ↓
Integrin activation
   ↓
Actomyosin tension
   ↓
Focal adhesion maturation
   ↓
More force transmission
   ↓
YAP/TAZ activation
   ↓
Gene expression
   ↓
ECM remodeling
   ↓
Further change in stiffness

This allows cells to adapt to and remodel their mechanical environment.

---

47. Key Mechanotransduction Molecules

Membrane

• Integrins
• Cadherins
• Piezo1
• Piezo2

Adhesion

• Talin
• Vinculin
• Kindlin
• FAK
• Src
• Paxillin

Cytoskeleton

• Actin
• Myosin II
• RhoA
• ROCK

Nuclear

• LINC complex
• SUN proteins
• KASH proteins
• Lamins

Transcriptional

• YAP
• TAZ
• TEAD

---

48. High-Yield Comparison of Mechanosensors

Mechanosensor	Mechanical input	Major response
Integrin	ECM force	Focal adhesion signaling
Cadherin	Cell–cell tension	Junctional signaling
Piezo1	Membrane tension	Ca²⁺ influx
Primary cilium	Fluid/mechanical stimuli	Signaling
Cytoskeleton	Force/tension	Remodeling
LINC complex	Nuclear force	Nuclear/chromatin response

---

49. Master’s-Level Concept: Mechanotransduction Is Bidirectional

The relationship between cell and environment is not one-way.

Cells sense mechanical properties and also change them.

ENVIRONMENT
    ↓
Mechanical sensing
    ↓
Cellular response
    ↓
Cytoskeletal force
    ↓
ECM remodeling
    ↓
ALTERED ENVIRONMENT
    ↓
New mechanical signal

Therefore, cells participate in a continuous mechanical feedback system with their surroundings.

---

50. Master’s-Level Concept: Mechanical Force Can Change Protein Conformation

Some mechanotransduction proteins behave as force-sensitive molecular switches.

Examples:

• Talin
• α-catenin
• Vinculin-associated complexes

The general principle is:

Mechanical force
       ↓
Protein deformation
       ↓
Hidden binding site exposed
       ↓
New protein interaction
       ↓
Signal amplification

This provides a direct molecular mechanism for sensing force.

---

51. Master’s-Level Concept: Mechanotransduction Can Reach the Genome

The complete pathway can be summarized:

EXTRACELLULAR FORCE
        ↓
MEMBRANE SENSOR
        ↓
ADHESION COMPLEX
        ↓
CYTOSKELETON
        ↓
LINC COMPLEX
        ↓
NUCLEAR LAMINA
        ↓
CHROMATIN
        ↓
TRANSCRIPTION
        ↓
CELL PHENOTYPE

This is one of the most important concepts linking cell biology, molecular biology and tissue mechanics.

---

52. Clinical and Research Importance

Mechanotransduction is relevant to:

• Cardiovascular biology
• Orthopedics
• Cancer biology
• Fibrosis
• Regenerative medicine
• Tissue engineering
• Stem-cell biology
• Neuroscience
• Vascular biology
• Developmental biology

It is particularly important when studying how cells respond to biomaterials and engineered tissue environments.

---

53. Short Examination Answer

Mechanotransduction

Mechanotransduction is the process by which cells convert mechanical stimuli into biochemical and cellular responses. Mechanical inputs include extracellular matrix stiffness, cell–cell tension, membrane tension, fluid shear stress, stretch and compression.

Major mechanosensors include integrins, cadherins, mechanosensitive ion channels such as Piezo1 and Piezo2, cytoskeletal structures, primary cilia and nuclear-envelope complexes. Integrins connect the extracellular matrix to actin through focal adhesion proteins such as talin, vinculin, FAK and paxillin. Mechanical force can induce conformational changes in proteins such as talin and α-catenin, leading to reinforcement of adhesion complexes.

Mechanosensitive Piezo channels convert membrane deformation into ion flux, particularly Ca²⁺ signaling. Mechanical tension also activates RhoA–ROCK–myosin pathways, producing actomyosin contractility. Mechanical information can be transmitted from the cytoskeleton to the nucleus through the LINC complex and nuclear lamina, influencing chromatin organization and transcription.

The YAP/TAZ pathway provides an important link between mechanical environment and gene expression. Increased matrix stiffness and cytoskeletal tension generally favor nuclear YAP/TAZ activity and transcriptional responses. Mechanotransduction therefore regulates cell shape, migration, proliferation, differentiation, tissue development, fibrosis and cancer progression.

---

54. Viva Questions

Q1. Define mechanotransduction.
Conversion of mechanical stimuli into biochemical and cellular responses.

Q2. Name two major mechanosensitive ion channels.
Piezo1 and Piezo2.

Q3. What is the role of integrins?
They connect the ECM to the intracellular cytoskeleton and transmit mechanical and biochemical signals.

Q4. Name important focal adhesion proteins.
Talin, vinculin, FAK, paxillin and kindlin.

Q5. What is the role of talin?
It links integrins to actin-associated machinery and functions as a force-sensitive protein.

Q6. What is the role of α-catenin?
It contributes to force transmission between cadherin complexes and the actin cytoskeleton.

Q7. What is Piezo1?
A mechanosensitive ion channel that responds to mechanical membrane deformation.

Q8. What is the major second messenger generated by Piezo activation?
Ca²⁺.

Q9. What is the RhoA–ROCK pathway?
A pathway promoting actomyosin contractility.

Q10. What are YAP and TAZ?
Mechanosensitive transcriptional coactivators regulated by the Hippo/mechanical signaling system.

Q11. What is the LINC complex?
A molecular bridge connecting the cytoskeleton to the nucleus.

Q12. How can ECM stiffness influence gene expression?
Through integrin signaling, cytoskeletal tension and pathways such as YAP/TAZ.

Q13. Why is mechanotransduction important in cancer?
Altered matrix stiffness and cellular tension can promote abnormal proliferation, survival and invasion.

Q14. What is mechanochemical feedback?
A process in which mechanical forces alter biochemical signaling, which subsequently changes the mechanical state of the cell.

---

55. One-Minute Revision

                         MECHANOTRANSDUCTION
                                  │
                    ┌─────────────┼─────────────┐
                    ↓             ↓             ↓
                 INTEGRIN      CADHERIN       PIEZO
                    │             │             │
                    ↓             ↓             ↓
                 TALIN        α-CATENIN         Ca²⁺
                    │             │             │
                    └─────────────┼─────────────┘
                                  ↓
                           ACTIN CYTOSKELETON
                                  │
                              RHOA / ROCK
                                  │
                              MYOSIN II
                                  │
                           CELLULAR TENSION
                                  │
                    ┌─────────────┴─────────────┐
                    ↓                           ↓
             FOCAL ADHESION                NUCLEUS
                    │                           │
                    │                      LINC COMPLEX
                    │                           │
                    └─────────────┬─────────────┘
                                  ↓
                              YAP / TAZ
                                  ↓
                              TEAD
                                  ↓
                           GENE EXPRESSION
                                  ↓
                       CELLULAR RESPONSE

Core memory rule

Integrin → ECM sensing
Cadherin → cell–cell force sensing
Piezo → mechanical force → Ca²⁺
Talin/α-catenin → force-sensitive adhesion proteins
RhoA–ROCK → actomyosin tension
LINC → cytoskeleton-to-nucleus force transmission
YAP/TAZ → mechanical regulation of transcription
Mechanotransduction = FORCE → SIGNAL → GENE EXPRESSION → CELL RESPONSE