Abstract

The 2021 Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3C) featured a workshop titled “The Elephant in the Room: Nuclear Mechanics and Mechanobiology.” The goal of this workshop was to provide a perspective from experts in the field on the current understanding of nuclear mechanics and its role in mechanobiology. This paper reviews the major themes and questions discussed during the workshop, including historical context on the initial methods of measuring the mechanical properties of the nucleus and classifying the primary structures dictating nuclear mechanics, physical plasticity of the nucleus, the emerging role of the linker of nucleoskeleton and cytoskeleton (LINC) complex in coupling the nucleus to the cytoplasm and driving the behavior of individual cells and multicellular assemblies, and the computational models currently in use to investigate the mechanisms of gene expression and cell signaling. Ongoing questions and controversies, along with promising future directions, are also discussed.

References

1.
Ambrosini
,
A.
,
Rayer
,
M.
,
Monier
,
B.
, and
Suzanne
,
M.
,
2019
, “
Mechanical Function of the Nucleus in Force Generation During Epithelial Morphogenesis
,”
Dev. Cell
,
50
(
2
), pp.
197
211.e5
.10.1016/j.devcel.2019.05.027
2.
Seelbinder
,
B.
,
Ghosh
,
S.
,
Schneider
,
S. E.
,
Scott
,
A. K.
,
Berman
,
A. G.
,
Goergen
,
C. J.
,
Margulies
,
K. B.
,
Bedi
,
K. C.
, Jr.
,
Casas
,
E.
,
Swearingen
,
A. R.
,
Brumbaugh
,
J.
,
Calve
,
S.
, and
Neu
,
C. P.
,
2021
, “
Nuclear Deformation Guides Chromatin Reorganization in Cardiac Development and Disease
,”
Nat. Biomed. Eng.
,
5
(
12
), pp.
1500
1516
.10.1038/s41551-021-00823-9
3.
Lavrushkina
,
S. V.
,
Ovsyannikova
,
N. L.
,
Yudina
,
A. S.
,
Strelkova
,
O. S.
,
Zhironkina
,
O. A.
,
Perepelina
,
K. I.
,
Malashicheva
,
A. B.
, and
Kireev
,
I. I.
,
2019
, “
The Role of Mechanical Properties of the Nucleus in Maintaining Tissue Homeostasis
,”
Cell Tissue Biol.
,
13
(
3
), pp.
237
241
.10.1134/S1990519X19030064
4.
Moss
,
S. F.
,
Krivosheyev
,
V.
,
de Souza
,
A.
,
Chin
,
K.
,
Gaetz
,
H. P.
,
Chaudhary
,
N.
,
Worman
,
H. J.
, and
Holt
,
P. R.
,
1999
, “
Decreased and Aberrant Nuclear Lamin Expression in Gastrointestinal Tract Neoplasms
,”
Gut
,
45
(
5
), pp.
723
729
.10.1136/gut.45.5.723
5.
Venables
,
R. S.
,
McLean
,
S.
,
Luny
,
D.
,
Moteleb
,
E.
,
Morley
,
S.
,
Quinlan
,
R. A.
,
Lane
,
E. B.
, and
Hutchison
,
C. J.
,
2001
, “
Expression of Individual Lamins in Basal Cell Carcinomas of the Skin
,”
Br. J. Cancer
,
84
(
4
), pp.
512
519
.10.1054/bjoc.2000.1632
6.
Tilli
,
C. M.
,
Ramaekers
,
F. C.
,
Broers
,
J. L.
,
Hutchison
,
C. J.
, and
Neumann
,
H. A.
,
2003
, “
Lamin Expression in Normal Human Skin, Actinic Keratosis, Squamous Cell Carcinoma and Basal Cell Carcinoma
,”
Br. J. Dermatol.
,
148
(
1
), pp.
102
109
.10.1046/j.1365-2133.2003.05026.x
7.
Martins
,
F.
,
Sousa
,
J.
,
Pereira
,
C. D.
,
Cruz e Silva
,
O. A. B.
, and
Rebelo
,
S.
,
2020
, “
Nuclear Envelope Dysfunction and Its Contribution to the Aging Process
,”
Aging Cell
,
19
(
5
), p.
e13143
.10.1111/acel.13143
8.
Phillip
,
J. M.
,
Aifuwa
,
I.
,
Walston
,
J.
, and
Wirtz
,
D.
,
2015
, “
The Mechanobiology of Aging
,”
Annu. Rev. Biomed. Eng.
,
17
(
1
), pp.
113
141
.10.1146/annurev-bioeng-071114-040829
9.
Sanchez-Adams
,
J.
,
Leddy
,
H. A.
,
McNulty
,
A. L.
,
O'Conor
,
C. J.
, and
Guilak
,
F.
,
2014
, “
The Mechanobiology of Articular Cartilage: Bearing the Burden of Osteoarthritis
,”
Curr. Rheumatol. Rep.
,
16
(
10
), p.
451
.10.1007/s11926-014-0451-6
10.
Clippinger
,
S. R.
,
Cloonan
,
P. E.
,
Greenberg
,
L.
,
Ernst
,
M.
,
Stump
,
W. T.
, and
Greenberg
,
M. J.
,
2019
, “
Disrupted Mechanobiology Links the Molecular and Cellular Phenotypes in Familial Dilated Cardiomyopathy
,”
Proc. Natl. Acad. Sci. U. S. A.
,
116
(
36
), pp.
17831
17840
.10.1073/pnas.1910962116
11.
Roy
,
B.
,
Yuan
,
L.
,
Lee
,
Y.
,
Bharti
,
A.
,
Mitra
,
A.
, and
Shivashankar
,
G. V.
,
2020
, “
Fibroblast Rejuvenation by Mechanical Reprogramming and Redifferentiation
,”
Proc. Natl. Acad. Sci. U. S. A.
,
117
(
19
), pp.
10131
10141
.10.1073/pnas.1911497117
12.
Szczesny
,
S. E.
, and
Mauck
,
R. L.
,
2017
, “
The Nuclear Option: Evidence Implicating the Cell Nucleus in Mechanotransduction
,”
ASME J. Biomech. Eng.
,
139
(
2
), p.
021006
.10.1115/1.4035350
13.
Lele
,
T. P.
,
Dickinson
,
R. B.
, and
Gundersen
,
G. G.
,
2018
, “
Mechanical Principles of Nuclear Shaping and Positioning
,”
J. Cell. Biol.
,
217
(
10
), pp.
3330
3342
.10.1083/jcb.201804052
14.
Miroshnikova
,
Y. A.
, and
Wickström
,
S. A.
,
2022
, “
Mechanical Forces in Nuclear Organization
,”
Cold Spring Harb. Perspect. Biol.
,
14
(
1
), p.
a039685
.10.1101/cshperspect.a039685
15.
Cho
,
S.
,
Irianto
,
J.
, and
Discher
,
D. E.
,
2017
, “
Mechanosensing by the Nucleus: From Pathways to Scaling Relationships
,”
J. Cell Biol.
,
216
(
2
), pp.
305
315
.10.1083/jcb.201610042
16.
Janota
,
C. S.
,
Calero-Cuenca
,
F. J.
, and
Gomes
,
E. R.
,
2020
, “
The Role of the Cell Nucleus in Mechanotransduction
,”
Curr. Opin. Cell Biol.
,
63
, pp.
204
211
.10.1016/j.ceb.2020.03.001
17.
Kirby
,
T. J.
, and
Lammerding
,
J.
,
2018
, “
Emerging Views of the Nucleus as a Cellular Mechanosensor
,”
Nat. Cell Biol.
,
20
(
4
), pp.
373
381
.10.1038/s41556-018-0038-y
18.
Pelling
,
A. E.
, and
Horton
,
M. A.
,
2008
, “
An Historical Perspective on Cell Mechanics
,”
Pflugers Arch.
,
456
(
1
), pp.
3
12
.10.1007/s00424-007-0405-1
19.
Lavrenyuk
,
K.
,
Conway
,
D.
, and
Dahl
,
K. N.
,
2021
, “
Imaging Methods in Mechanosensing: A Historical Perspective and Visions for the Future
,”
Mol. Biol. Cell
,
32
(
9
), pp.
842
854
.10.1091/mbc.E20-10-0671
20.
Wang
,
J. H.
, and
Li
,
B.
,
2009
, “
Application of Cell Traction Force Microscopy for Cell Biology Research
,”
Methods Mol. Biol.
,
586
, pp.
301
313
.10.1007/978-1-60761-376-3
21.
Caille
,
N.
,
Thoumine
,
O.
,
Tardy
,
Y.
, and
Meister
,
J. J.
,
2002
, “
Contribution of the Nucleus to the Mechanical Properties of Endothelial Cells
,”
J. Biomech.
,
35
(
2
), pp.
177
187
.10.1016/S0021-9290(01)00201-9
22.
Guilak
,
F.
,
1995
, “
Compression-Induced Changes in the Shape and Volume of the Chondrocyte Nucleus
,”
J. Biomech.
,
28
(
12
), pp.
1529
1541
.10.1016/0021-9290(95)00100-X
23.
Kan
,
H. C.
,
Shyy
,
W.
,
Udaykumar
,
H. S.
,
Vigneron
,
P.
, and
Tran-Son-Tay
,
R.
,
1999
, “
Effects of Nucleus on Leukocyte Recovery
,”
Ann. Biomed. Eng.
,
27
(
5
), pp.
648
655
.10.1114/1.214
24.
Aebi
,
U.
,
Cohn
,
J.
,
Buhle
,
L.
, and
Gerace
,
L.
,
1986
, “
The Nuclear Lamina is a Meshwork of Intermediate-Type Filaments
,”
Nature
,
323
(
6088
), pp.
560
564
.10.1038/323560a0
25.
Dahl
,
K. N.
,
Engler
,
A. J.
,
Pajerowski
,
J. D.
, and
Discher
,
D. E.
,
2005
, “
Power-Law Rheology of Isolated Nuclei With Deformation Mapping of Nuclear Substructures
,”
Biophys. J.
,
89
(
4
), pp.
2855
2864
.10.1529/biophysj.105.062554
26.
Vaziri
,
A.
, and
Mofrad
,
M. R.
,
2007
, “
Mechanics and Deformation of the Nucleus in Micropipette Aspiration Experiment
,”
J. Biomech.
,
40
(
9
), pp.
2053
2062
.10.1016/j.jbiomech.2006.09.023
27.
Dahl
,
K. N.
, and
Kalinowski
,
A.
,
2011
, “
Nucleoskeleton Mechanics at a Glance
,”
J. Cell Sci.
,
124
(
5
), pp.
675
678
.10.1242/jcs.069096
28.
Dahl
,
K. N.
,
Ribeiro
,
A. J.
, and
Lammerding
,
J.
,
2008
, “
Nuclear Shape, Mechanics, and Mechanotransduction
,”
Circ. Res.
,
102
(
11
), pp.
1307
1318
.10.1161/CIRCRESAHA.108.173989
29.
Capell
,
B. C.
, and
Collins
,
F. S.
,
2006
, “
Human Laminopathies: Nuclei Gone Genetically Awry
,”
Nat. Rev. Genet.
,
7
(
12
), pp.
940
952
.10.1038/nrg1906
30.
Gruenbaum
,
Y.
,
Margalit
,
A.
,
Goldman
,
R. D.
,
Shumaker
,
D. K.
, and
Wilson
,
K. L.
,
2005
, “
The Nuclear Lamina Comes of Age
,”
Nat. Rev. Mol. Cell Biol.
,
6
(
1
), pp.
21
31
.10.1038/nrm1550
31.
Lammerding
,
J.
,
Fong
,
L. G.
,
Ji
,
J. Y.
,
Reue
,
K.
,
Stewart
,
C. L.
,
Young
,
S. G.
, and
Lee
,
R. T.
,
2006
, “
Lamins a and C but Not Lamin B1 Regulate Nuclear Mechanics
,”
J. Biol. Chem.
,
281
(
35
), pp.
25768
25780
.10.1074/jbc.M513511200
32.
Prokocimer
,
M.
,
Davidovich
,
M.
,
Nissim-Rafinia
,
M.
,
Wiesel-Motiuk
,
N.
,
Bar
,
D. Z.
,
Barkan
,
R.
,
Meshorer
,
E.
, and
Gruenbaum
,
Y.
,
2009
, “
Nuclear Lamins: Key Regulators of Nuclear Structure and Activities
,”
J. Cell Mol. Med.
,
13
(
6
), pp.
1059
1085
.10.1111/j.1582-4934.2008.00676.x
33.
Schäpe
,
J.
,
Prauße
,
S.
,
Radmacher
,
M.
, and
Stick
,
R.
,
2009
, “
Influence of Lamin a on the Mechanical Properties of Amphibian Oocyte Nuclei Measured by Atomic Force Microscopy
,”
Biophys. J.
,
96
(
10
), pp.
4319
4325
.10.1016/j.bpj.2009.02.048
34.
Coffinier
,
C.
,
Chang
,
S. Y.
,
Nobumori
,
C.
,
Tu
,
Y.
,
Farber
,
E. A.
,
Toth
,
J. I.
,
Fong
,
L. G.
, and
Young
,
S. G.
,
2010
, “
Abnormal Development of the Cerebral Cortex and Cerebellum in the Setting of Lamin B2 Deficiency
,”
Proc. Natl. Acad. Sci. U. S. A.
,
107
(
11
), pp.
5076
5081
.10.1073/pnas.0908790107
35.
Tang
,
C. W.
,
Maya-Mendoza
,
A.
,
Martin
,
C.
,
Zeng
,
K.
,
Chen
,
S.
,
Feret
,
D.
,
Wilson
,
S. A.
, and
Jackson
,
D. A.
,
2008
, “
The Integrity of a Lamin-B1-Dependent Nucleoskeleton is a Fundamental Determinant of RNA Synthesis in Human Cells
,”
J. Cell Sci.
,
121
(
7
), pp.
1014
1024
.10.1242/jcs.020982
36.
Turgay
,
Y.
,
Eibauer
,
M.
,
Goldman
,
A. E.
,
Shimi
,
T.
,
Khayat
,
M.
,
Ben-Harush
,
K.
,
Dubrovsky-Gaupp
,
A.
,
Sapra
,
K. T.
,
Goldman
,
R. D.
, and
Medalia
,
O.
,
2017
, “
The Molecular Architecture of Lamins in Somatic Cells
,”
Nature
,
543
(
7644
), pp.
261
264
.10.1038/nature21382
37.
Nmezi
,
B.
,
Xu
,
J.
,
Fu
,
R.
,
Armiger
,
T. J.
,
Rodriguez-Bey
,
G.
,
Powell
,
J. S.
,
Ma
,
H.
,
Sullivan
,
M.
,
Tu
,
Y.
,
Chen
,
N. Y.
,
Young
,
S. G.
,
Stolz
,
D. B.
,
Dahl
,
K. N.
,
Liu
,
Y.
, and
Padiath
,
Q. S.
,
2019
, “
Concentric Organization of A- and B-Type Lamins Predicts Their Distinct Roles in the Spatial Organization and Stability of the Nuclear Lamina
,”
Proc. Natl. Acad. Sci. U. S. A.
,
116
(
10
), pp.
4307
4315
.10.1073/pnas.1810070116
38.
Stierlé
,
V.
,
Couprie
,
J.
,
Ostlund
,
C.
,
Krimm
,
I.
,
Zinn-Justin
,
S.
,
Hossenlopp
,
P.
,
Worman
,
H. J.
,
Courvalin
,
J. C.
, and
Duband-Goulet
,
I.
,
2003
, “
The Carboxyl-Terminal Region Common to Lamins A and C Contains a DNA Binding Domain
,”
Biochemistry
,
42
(
17
), pp.
4819
4828
.10.1021/bi020704g
39.
Stephens
,
A. D.
,
Liu
,
P. Z.
,
Kandula
,
V.
,
Chen
,
H.
,
Almassalha
,
L. M.
,
Herman
,
C.
,
Backman
,
V.
,
O'Halloran
,
T.
,
Adam
,
S. A.
,
Goldman
,
R. D.
,
Banigan
,
E. J.
, and
Marko
,
J. F.
,
2019
, “
Physicochemical Mechanotransduction Alters Nuclear Shape and Mechanics Via Heterochromatin Formation
,”
Mol. Biol. Cell
,
30
(
17
), pp.
2320
2330
.10.1091/mbc.E19-05-0286
40.
Spagnol
,
S. T.
, and
Dahl
,
K. N.
,
2014
, “
Active Cytoskeletal Force and Chromatin Condensation Independently Modulate Intranuclear Network Fluctuations
,”
Integr. Biol.
,
6
(
5
), pp.
523
531
.10.1039/C3IB40226F
41.
Lombardi
,
M. L.
,
Jaalouk
,
D. E.
,
Shanahan
,
C. M.
,
Burke
,
B.
,
Roux
,
K. J.
, and
Lammerding
,
J.
,
2011
, “
The Interaction Between Nesprins and Sun Proteins at the Nuclear Envelope is Critical for Force Transmission Between the Nucleus and Cytoskeleton
,”
J. Biol. Chem.
,
286
(
30
), pp.
26743
26753
.10.1074/jbc.M111.233700
42.
Alam
,
S. G.
,
Lovett
,
D.
,
Kim
,
D. I.
,
Roux
,
K. J.
,
Dickinson
,
R. B.
, and
Lele
,
T. P.
,
2015
, “
The Nucleus is an Intracellular Propagator of Tensile Forces in NIH 3T3 Fibroblasts
,”
J. Cell Sci.
,
128
(
10
), pp.
1901
1911
.10.1242/jcs.161703
43.
Enyedi
,
B.
,
Jelcic
,
M.
, and
Niethammer
,
P.
,
2016
, “
The Cell Nucleus Serves as a Mechanotransducer of Tissue Damage-Induced Inflammation
,”
Cell
,
165
(
5
), pp.
1160
1170
.10.1016/j.cell.2016.04.016
44.
Elosegui-Artola
,
A.
,
Andreu
,
I.
,
Beedle
,
A. E. M.
,
Lezamiz
,
A.
,
Uroz
,
M.
,
Kosmalska
,
A. J.
,
Oria
,
R.
,
Kechagia
,
J. Z.
,
Rico-Lastres
,
P.
,
Le Roux
,
A. L.
,
Shanahan
,
C. M.
,
Trepat
,
X.
,
Navajas
,
D.
,
Garcia-Manyes
,
S.
, and
Roca-Cusachs
,
P.
,
2017
, “
Force Triggers Yap Nuclear Entry by Regulating Transport Across Nuclear Pores
,”
Cell
,
171
(
6
), pp.
1397
1410.e14
.10.1016/j.cell.2017.10.008
45.
Wolf
,
K.
,
Te Lindert
,
M.
,
Krause
,
M.
,
Alexander
,
S.
,
Te Riet
,
J.
,
Willis
,
A. L.
,
Hoffman
,
R. M.
,
Figdor
,
C. G.
,
Weiss
,
S. J.
, and
Friedl
,
P.
,
2013
, “
Physical Limits of Cell Migration: Control by ECM Space and Nuclear Deformation and Tuning by Proteolysis and Traction Force
,”
J. Cell Biol.
,
201
(
7
), pp.
1069
1084
.10.1083/jcb.201210152
46.
Olins
,
A. L.
,
Herrmann
,
H.
,
Lichter
,
P.
,
Kratzmeier
,
M.
,
Doenecke
,
D.
, and
Olins
,
D. E.
,
2001
, “
Nuclear Envelope and Chromatin Compositional Differences Comparing Undifferentiated and Retinoic Acid- and Phorbol Ester-Treated HL-60 Cells
,”
Exp. Cell Res.
,
268
(
2
), pp.
115
127
.10.1006/excr.2001.5269
47.
Olins
,
A. L.
,
Hoang
,
T. V.
,
Zwerger
,
M.
,
Herrmann
,
H.
,
Zentgraf
,
H.
,
Noegel
,
A. A.
,
Karakesisoglou
,
I.
,
Hodzic
,
D.
, and
Olins
,
D. E.
,
2009
, “
The LINC-Less Granulocyte Nucleus
,”
Eur. J. Cell Biol.
,
88
(
4
), pp.
203
214
.10.1016/j.ejcb.2008.10.001
48.
Denais
,
C. M.
,
Gilbert
,
R. M.
,
Isermann
,
P.
,
McGregor
,
A. L.
,
Te Lindert
,
M.
,
Weigelin
,
B.
,
Davidson
,
P. M.
,
Friedl
,
P.
,
Wolf
,
K.
, and
Lammerding
,
J.
,
2016
, “
Nuclear Envelope Rupture and Repair During Cancer Cell Migration
,”
Science
,
352
(
6283
), pp.
353
358
.10.1126/science.aad7297
49.
Irianto
,
J.
,
Xia
,
Y.
,
Pfeifer
,
C. R.
,
Athirasala
,
A.
,
Ji
,
J.
,
Alvey
,
C.
,
Tewari
,
M.
,
Bennett
,
R. R.
,
Harding
,
S. M.
,
Liu
,
A. J.
,
Greenberg
,
R. A.
, and
Discher
,
D. E.
,
2017
, “
DNA Damage Follows Repair Factor Depletion and Portends Genome Variation in Cancer Cells After Pore Migration
,”
Curr. Biol.
,
27
(
2
), pp.
210
223
.10.1016/j.cub.2016.11.049
50.
Pfeifer
,
C. R.
,
Xia
,
Y.
,
Zhu
,
K.
,
Liu
,
D.
,
Irianto
,
J.
,
García
,
V. M. M.
,
Millán
,
L. M. S.
,
Niese
,
B.
,
Harding
,
S.
,
Deviri
,
D.
,
Greenberg
,
R. A.
, and
Discher
,
D. E.
,
2018
, “
Constricted Migration Increases DNA Damage and Independently Represses Cell Cycle
,”
Mol. Biol. Cell
,
29
(
16
), pp.
1948
1962
.10.1091/mbc.E18-02-0079
51.
Maciejowski
,
J.
, and
Hatch
,
E. M.
,
2020
, “
Nuclear Membrane Rupture and Its Consequences
,”
Annu. Rev. Cell Dev. Biol.
,
36
(
1
), pp.
85
114
.10.1146/annurev-cellbio-020520-120627
52.
Versaevel
,
M.
,
Grevesse
,
T.
, and
Gabriele
,
S.
,
2012
, “
Spatial Coordination Between Cell and Nuclear Shape Within Micropatterned Endothelial Cells
,”
Nat Commun.
,
3
(
1
), p.
671
.10.1038/ncomms1668
53.
Alisafaei
,
F.
,
Jokhun
,
D. S.
,
Shivashankar
,
G. V.
, and
Shenoy
,
V. B.
,
2019
, “
Regulation of Nuclear Architecture, Mechanics, and Nucleocytoplasmic Shuttling of Epigenetic Factors by Cell Geometric Constraints
,”
Proc. Natl. Acad. Sci. U. S. A.
,
116
(
27
), pp.
13200
13209
.10.1073/pnas.1902035116
54.
Tocco
,
V. J.
,
Li
,
Y.
,
Christopher
,
K. G.
,
Matthews
,
J. H.
,
Aggarwal
,
V.
,
Paschall
,
L.
,
Luesch
,
H.
,
Licht
,
J. D.
,
Dickinson
,
R. B.
, and
Lele
,
T. P.
,
2018
, “
The Nucleus is Irreversibly Shaped by Motion of Cell Boundaries in Cancer and Non-Cancer Cells
,”
J. Cell Physiol.
,
233
(
2
), pp.
1446
1454
.10.1002/jcp.26031
55.
Dahl
,
K. N.
,
Kahn
,
S. M.
,
Wilson
,
K. L.
, and
Discher
,
D. E.
,
2004
, “
The Nuclear Envelope Lamina Network Has Elasticity and a Compressibility Limit Suggestive of a Molecular Shock Absorber
,”
J. Cell Sci.
,
117
(
20
), pp.
4779
4786
.10.1242/jcs.01357
56.
Finan
,
J. D.
,
Chalut
,
K. J.
,
Wax
,
A.
, and
Guilak
,
F.
,
2009
, “
Nonlinear Osmotic Properties of the Cell Nucleus
,”
Ann. Biomed. Eng.
,
37
(
3
), pp.
477
491
.10.1007/s10439-008-9618-5
57.
Finan
,
J. D.
, and
Guilak
,
F.
,
2010
, “
The Effects of Osmotic Stress on the Structure and Function of the Cell Nucleus
,”
J. Cell Biochem.
,
109
(
3
), pp.
460
467
.10.1002/jcb.22437
58.
Finan
,
J. D.
,
Leddy
,
H. A.
, and
Guilak
,
F.
,
2011
, “
Osmotic Stress Alters Chromatin Condensation and Nucleocytoplasmic Transport
,”
Biochem. Biophys. Res. Commun.
,
408
(
2
), pp.
230
235
.10.1016/j.bbrc.2011.03.131
59.
Li
,
Y.
,
Lovett
,
D.
,
Zhang
,
Q.
,
Neelam
,
S.
,
Kuchibhotla
,
R. A.
,
Zhu
,
R.
,
Gundersen
,
G. G.
,
Lele
,
T. P.
, and
Dickinson
,
R. B.
,
2015
, “
Moving Cell Boundaries Drive Nuclear Shaping During Cell Spreading
,”
Biophys. J.
,
109
(
4
), pp.
670
686
.10.1016/j.bpj.2015.07.006
60.
Lomakin
,
A. J.
,
Cattin
,
C. J.
,
Cuvelier
,
D.
,
Alraies
,
Z.
,
Molina
,
M.
,
Nader
,
G. P. F.
,
Srivastava
,
N.
,
Sáez
,
P. J.
,
Garcia-Arcos
,
J. M.
,
Zhitnyak
,
I. Y.
,
Bhargava
,
A.
,
Driscoll
,
M. K.
,
Welf
,
E. S.
,
Fiolka
,
R.
,
Petrie
,
R. J.
,
De Silva
,
N. S.
,
González-Granado
,
J. M.
,
Manel
,
N.
,
Lennon-Duménil
,
A. M.
,
Müller
,
D. J.
, and
Piel
,
M.
,
2020
, “
The Nucleus Acts as a Ruler Tailoring Cell Responses to Spatial Constraints
,”
Science
,
370
(
6514
), p.
eaba2894
.10.1126/science.aba2894
61.
Davidson
,
P. M.
,
Sliz
,
J.
,
Isermann
,
P.
,
Denais
,
C.
, and
Lammerding
,
J.
,
2015
, “
Design of a Microfluidic Device to Quantify Dynamic Intra-Nuclear Deformation During Cell Migration Through Confining Environments
,”
Integr. Biol.
,
7
(
12
), pp.
1534
1546
.10.1039/C5IB00200A
62.
Neelam
,
S.
,
Hayes
,
P. R.
,
Zhang
,
Q.
,
Dickinson
,
R. B.
, and
Lele
,
T. P.
,
2016
, “
Vertical Uniformity of Cells and Nuclei in Epithelial Monolayers
,”
Sci. Rep.
,
6
(
1
), p.
19689
.10.1038/srep19689
63.
Cosgrove
,
B. D.
,
Loebel
,
C.
,
Driscoll
,
T. P.
,
Tsinman
,
T. K.
,
Dai
,
E. N.
,
Heo
,
S. J.
,
Dyment
,
N. A.
,
Burdick
,
J. A.
, and
Mauck
,
R. L.
,
2021
, “
Nuclear Envelope Wrinkling Predicts Mesenchymal Progenitor Cell Mechano-Response in 2D and 3D Microenvironments
,”
Biomaterials
,
270
, p.
120662
.10.1016/j.biomaterials.2021.120662
64.
Dickinson
,
R. B.
,
Katiyar
,
A.
,
Dubell
,
C. R.
, and
Lele
,
T. P.
,
2022
, “
Viscous Shaping of the Compliant Cell Nucleus
,”
APL Bioeng.
,
6
(
1
), p.
010901
.10.1063/5.0071652
65.
Armiger
,
T. J.
,
Lampi
,
M. C.
,
Reinhart-King
,
C. A.
, and
Dahl
,
K. N.
,
2018
, “
Determining Mechanical Features of Modulated Epithelial Monolayers Using Subnuclear Particle Tracking
,”
J. Cell Sci.
,
131
(
12
), p. jcs216010.10.1242/jcs.216010
66.
Bouzid
,
T.
,
Kim
,
E.
,
Riehl
,
B. D.
,
Esfahani
,
A. M.
,
Rosenbohm
,
J.
,
Yang
,
R.
,
Duan
,
B.
, and
Lim
,
J. Y.
,
2019
, “
The LINC Complex, Mechanotransduction, and Mesenchymal Stem Cell Function and Fate
,”
J. Biol. Eng.
,
13
(
1
), p.
68
.10.1186/s13036-019-0197-9
67.
Maniotis
,
A. J.
,
Chen
,
C. S.
, and
Ingber
,
D. E.
,
1997
, “
Demonstration of Mechanical Connections Between Integrins, Cytoskeletal Filaments, and Nucleoplasm That Stabilize Nuclear Structure
,”
Proc. Natl. Acad. Sci. U. S. A.
,
94
(
3
), pp.
849
854
.10.1073/pnas.94.3.849
68.
Fedorchak
,
G.
, and
Lammerding
,
J.
,
2016
, “
Cell Microharpooning to Study Nucleo-Cytoskeletal Coupling
,”
Methods Mol. Biol.
,
1411
, pp.
241
254
.10.1007/978-1-4939-3530-7
69.
Arsenovic
,
P. T.
,
Ramachandran
,
I.
,
Bathula
,
K.
,
Zhu
,
R.
,
Narang
,
J. D.
,
Noll
,
N. A.
,
Lemmon
,
C. A.
,
Gundersen
,
G. G.
, and
Conway
,
D. E.
,
2016
, “
Nesprin-2G, a Component of the Nuclear LINC Complex, Is Subject to Myosin-Dependent Tension
,”
Biophys. J.
,
110
(
1
), pp.
34
43
.10.1016/j.bpj.2015.11.014
70.
Borghi
,
N.
,
Sorokina
,
M.
,
Shcherbakova
,
O. G.
,
Weis
,
W. I.
,
Pruitt
,
B. L.
,
Nelson
,
W. J.
, and
Dunn
,
A. R.
,
2012
, “
E-Cadherin is Under Constitutive Actomyosin-Generated Tension That is Increased at Cell-Cell Contacts Upon Externally Applied Stretch
,”
Proc. Natl. Acad. Sci. U. S. A.
,
109
(
31
), pp.
12568
12573
.10.1073/pnas.1204390109
71.
Cai
,
D.
,
Chen
,
S. C.
,
Prasad
,
M.
,
He
,
L.
,
Wang
,
X.
,
Choesmel-Cadamuro
,
V.
,
Sawyer
,
J. K.
,
Danuser
,
G.
, and
Montell
,
D. J.
,
2014
, “
Mechanical Feedback Through E-Cadherin Promotes Direction Sensing During Collective Cell Migration
,”
Cell
,
157
(
5
), pp.
1146
1159
.10.1016/j.cell.2014.03.045
72.
Conway
,
D. E.
,
Breckenridge
,
M. T.
,
Hinde
,
E.
,
Gratton
,
E.
,
Chen
,
C. S.
, and
Schwartz
,
M. A.
,
2013
, “
Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension Across VE-Cadherin and PECAM-1
,”
Curr. Biol.
,
23
(
11
), pp.
1024
1030
.10.1016/j.cub.2013.04.049
73.
Grashoff
,
C.
,
Hoffman
,
B. D.
,
Brenner
,
M. D.
,
Zhou
,
R.
,
Parsons
,
M.
,
Yang
,
M. T.
,
McLean
,
M. A.
,
Sligar
,
S. G.
,
Chen
,
C. S.
,
Ha
,
T.
, and
Schwartz
,
M. A.
,
2010
, “
Measuring Mechanical Tension Across Vinculin Reveals Regulation of Focal Adhesion Dynamics
,”
Nature
,
466
(
7303
), pp.
263
266
.10.1038/nature09198
74.
Déjardin
,
T.
,
Carollo
,
P. S.
,
Sipieter
,
F.
,
Davidson
,
P. M.
,
Seiler
,
C.
,
Cuvelier
,
D.
,
Cadot
,
B.
,
Sykes
,
C.
,
Gomes
,
E. R.
, and
Borghi
,
N.
,
2020
, “
Nesprins Are Mechanotransducers That Discriminate Epithelial-Mesenchymal Transition Programs
,”
J. Cell Biol.
,
219
(
10
), p. e201908036.10.1083/jcb.201908036
75.
Carley
,
E.
,
Stewart
,
R. M.
,
Zieman
,
A.
,
Jalilian
,
I.
,
King
,
D. E.
,
Zubek
,
A.
,
Lin
,
S.
,
Horsley
,
V.
, and
King
,
M. C.
,
2021
, “
The LINC Complex Transmits Integrin-Dependent Tension to the Nuclear Lamina and Represses Epidermal Differentiation
,”
Elife
,
10
, p. e58541.10.7554/eLife.58541
76.
Davidson
,
P. M.
,
Battistella
,
A.
,
Déjardin
,
T.
,
Betz
,
T.
,
Plastino
,
J.
,
Borghi
,
N.
,
Cadot
,
B.
, and
Sykes
,
C.
,
2020
, “
Nesprin-2 Accumulates at the Front of the Nucleus During Confined Cell Migration
,”
EMBO Rep.
,
21
(
7
), p.
e49910
.10.15252/embr.201949910
77.
Petrie
,
R. J.
,
Harlin
,
H. M.
,
Korsak
,
L. I.
, and
Yamada
,
K. M.
,
2017
, “
Activating the Nuclear Piston Mechanism of 3D Migration in Tumor Cells
,”
J. Cell Biol.
,
216
(
1
), pp.
93
100
.10.1083/jcb.201605097
78.
Petrie
,
R. J.
, and
Yamada
,
K. M.
,
2016
, “
Multiple Mechanisms of 3D Migration: The Origins of Plasticity
,”
Curr. Opin. Cell Biol.
,
42
, pp.
7
12
.10.1016/j.ceb.2016.03.025
79.
Luxton
,
G. W.
,
Gomes
,
E. R.
,
Folker
,
E. S.
,
Vintinner
,
E.
, and
Gundersen
,
G. G.
,
2010
, “
Linear Arrays of Nuclear Envelope Proteins Harness Retrograde Actin Flow for Nuclear Movement
,”
Science
,
329
(
5994
), pp.
956
959
.10.1126/science.1189072
80.
Wang
,
N.
,
Tytell
,
J. D.
, and
Ingber
,
D. E.
,
2009
, “
Mechanotransduction at a Distance: Mechanically Coupling the Extracellular Matrix With the Nucleus
,”
Nat. Rev. Mol. Cell Biol.
,
10
(
1
), pp.
75
82
.10.1038/nrm2594
81.
Tajik
,
A.
,
Zhang
,
Y.
,
Wei
,
F.
,
Sun
,
J.
,
Jia
,
Q.
,
Zhou
,
W.
,
Singh
,
R.
,
Khanna
,
N.
,
Belmont
,
A. S.
, and
Wang
,
N.
,
2016
, “
Transcription Upregulation Via Force-Induced Direct Stretching of Chromatin
,”
Nat. Mater.
,
15
(
12
), pp.
1287
1296
.10.1038/nmat4729
82.
Andreu
,
I.
,
Granero-Moya
,
I.
,
Chahare
,
N. R.
,
Clein
,
K.
,
Jordán
,
M.
,
Beedle
,
A. E. M.
,
Elosegui-Artola
,
A.
,
Trepat
,
X.
,
Raveh
,
B.
, and
Roca-Cusachs
,
P.
,
2021
, “
Mechanosensitivity of Nucleocytoplasmic Transport
,”
bioRxiv
, epub.10.1101/2021.07.23.453478
83.
Shiu
,
J. Y.
,
Aires
,
L.
,
Lin
,
Z.
, and
Vogel
,
V.
,
2018
, “
Nanopillar Force Measurements Reveal Actin-Cap-Mediated Yap Mechanotransduction
,”
Nat. Cell Biol.
,
20
(
3
), pp.
262
271
.10.1038/s41556-017-0030-y
84.
Denis
,
K. B.
,
Cabe
,
J. I.
,
Danielsson
,
B. E.
,
Tieu
,
K. V.
,
Mayer
,
C. R.
, and
Conway
,
D. E.
,
2021
, “
The LINC Complex is Required for Endothelial Cell Adhesion and Adaptation to Shear Stress and Cyclic Stretch
,”
Mol. Biol. Cell
,
32
(
18
), pp.
1654
1663
.10.1091/mbc.E20-11-0698
85.
Liu
,
Z.
,
Tan
,
J. L.
,
Cohen
,
D. M.
,
Yang
,
M. T.
,
Sniadecki
,
N. J.
,
Ruiz
,
S. A.
,
Nelson
,
C. M.
, and
Chen
,
C. S.
,
2010
, “
Mechanical Tugging Force Regulates the Size of Cell-Cell Junctions
,”
Proc. Natl. Acad. Sci. U. S. A.
,
107
(
22
), pp.
9944
9949
.10.1073/pnas.0914547107
86.
Maruthamuthu
,
V.
,
Sabass
,
B.
,
Schwarz
,
U. S.
, and
Gardel
,
M. L.
,
2011
, “
Cell-ECM Traction Force Modulates Endogenous Tension at Cell-Cell Contacts
,”
Proc. Natl. Acad. Sci. U. S. A.
,
108
(
12
), pp.
4708
4713
.10.1073/pnas.1011123108
87.
Zhang
,
Q.
,
Narayanan
,
V.
,
Mui
,
K. L.
,
O'Bryan
,
C. S.
,
Anderson
,
R. H.
,
Kc
,
B.
,
Cabe
,
J. I.
,
Denis
,
K. B.
,
Antoku
,
S.
,
Roux
,
K. J.
,
Dickinson
,
R. B.
,
Angelini
,
T. E.
,
Gundersen
,
G. G.
,
Conway
,
D. E.
, and
Lele
,
T. P.
,
2019
, “
Mechanical Stabilization of the Glandular Acinus by Linker of Nucleoskeleton and Cytoskeleton Complex
,”
Curr. Biol.
,
29
(
17
), pp.
2826
2839.e4
.10.1016/j.cub.2019.07.021
88.
Paszek
,
M. J.
, and
Weaver
,
V. M.
,
2004
, “
The Tension Mounts: Mechanics Meets Morphogenesis and Malignancy
,”
J. Mammary Gland Biol. Neoplasia
,
9
(
4
), pp.
325
342
.10.1007/s10911-004-1404-x
89.
Gupta
,
S.
,
Marcel
,
N.
,
Sarin
,
A.
, and
Shivashankar
,
G. V.
,
2012
, “
Role of Actin Dependent Nuclear Deformation in Regulating Early Gene Expression
,”
PLoS One
,
7
(
12
), p.
e53031
.10.1371/journal.pone.0053031
90.
Jain
,
N.
,
Iyer
,
K. V.
,
Kumar
,
A.
, and
Shivashankar
,
G. V.
,
2013
, “
Cell Geometric Constraints Induce Modular Gene-Expression Patterns Via Redistribution of HDAC3 Regulated by Actomyosin Contractility
,”
Proc. Natl. Acad. Sci. U. S. A.
,
110
(
28
), pp.
11349
11354
.10.1073/pnas.1300801110
91.
Ghosh
,
S.
,
Cuevas
,
V. C.
,
Seelbinder
,
B.
, and
Neu
,
C. P.
,
2021
, “
Image-Based Elastography of Heterochromatin and Euchromatin Domains in the Deforming Cell Nucleus
,”
Small
,
17
(
5
), p.
e2006109
.10.1002/smll.202006109
92.
Shenoy
,
V. B.
,
Wang
,
H.
, and
Wang
,
X.
,
2016
, “
A Chemo-Mechanical Free-Energy-Based Approach to Model Durotaxis and Extracellular Stiffness-Dependent Contraction and Polarization of Cells
,”
Interface Focus
,
6
(
1
), p.
20150067
.10.1098/rsfs.2015.0067
93.
Ahmadzadeh
,
H.
,
Webster
,
M. R.
,
Behera
,
R.
,
Jimenez Valencia
,
A. M.
,
Wirtz
,
D.
,
Weeraratna
,
A. T.
, and
Shenoy
,
V. B.
,
2017
, “
Modeling the Two-Way Feedback Between Contractility and Matrix Realignment Reveals a Nonlinear Mode of Cancer Cell Invasion
,”
Proc. Natl. Acad. Sci. U. S. A.
,
114
(
9
), pp.
E1617
E1626
.10.1073/pnas.1617037114
94.
Cao
,
P.
,
Short
,
M. P.
, and
Yip
,
S.
,
2017
, “
Understanding the Mechanisms of Amorphous Creep Through Molecular Simulation
,”
Proc. Natl. Acad. Sci. U. S. A.
,
114
(
52
), pp.
13631
13636
.10.1073/pnas.1708618114
95.
Seo
,
B. R.
,
Chen
,
X.
,
Ling
,
L.
,
Song
,
Y. H.
,
Shimpi
,
A. A.
,
Choi
,
S.
,
Gonzalez
,
J.
,
Sapudom
,
J.
,
Wang
,
K.
,
Andresen Eguiluz
,
R. C.
,
Gourdon
,
D.
,
Shenoy
,
V. B.
, and
Fischbach
,
C.
,
2020
, “
Collagen Microarchitecture Mechanically Controls Myofibroblast Differentiation
,”
Proc. Natl. Acad. Sci. U. S. A.
,
117
(
21
), pp.
11387
11398
.10.1073/pnas.1919394117
96.
Damodaran
,
K.
,
Venkatachalapathy
,
S.
,
Alisafaei
,
F.
,
Radhakrishnan
,
A. V.
,
Sharma Jokhun
,
D.
,
Shenoy
,
V. B.
, and
Shivashankar
,
G. V.
,
2018
, “
Compressive Force Induces Reversible Chromatin Condensation and Cell Geometry-Dependent Transcriptional Response
,”
Mol. Biol. Cell
,
29
(
25
), pp.
3039
3051
.10.1091/mbc.E18-04-0256
97.
Gong
,
Z.
,
Wisdom
,
K. M.
,
McEvoy
,
E.
,
Chang
,
J.
,
Adebowale
,
K.
,
Price
,
C. C.
,
Chaudhuri
,
O.
, and
Shenoy
,
V. B.
,
2021
, “
Recursive Feedback Between Matrix Dissipation and Chemo-Mechanical Signaling Drives Oscillatory Growth of Cancer Cell Invadopodia
,”
Cell Rep.
,
35
(
4
), p.
109047
.10.1016/j.celrep.2021.109047
98.
Lee
,
H. P.
,
Alisafaei
,
F.
,
Adebawale
,
K.
,
Chang
,
J.
,
Shenoy
,
V. B.
, and
Chaudhuri
,
O.
,
2021
, “
The Nuclear Piston Activates Mechanosensitive Ion Channels to Generate Cell Migration Paths in Confining Microenvironments
,”
Sci. Adv.
,
7
(
2
), p. eabd4058.10.1126/sciadv.abd4058
99.
Heo
,
S. J.
,
Song
,
K. H.
,
Thakur
,
S.
,
Miller
,
L. M.
,
Cao
,
X.
,
Peredo
,
A. P.
,
Seiber
,
B. N.
,
Qu
,
F.
,
Driscoll
,
T. P.
,
Shenoy
,
V. B.
,
Lakadamyali
,
M.
,
Burdick
,
J. A.
, and
Mauck
,
R. L.
,
2020
, “
Nuclear Softening Expedites Interstitial Cell Migration in Fibrous Networks and Dense Connective Tissues
,”
Sci. Adv.
,
6
(
25
), p.
eaax5083
.10.1126/sciadv.aax5083
You do not currently have access to this content.