Background: The motion and redistribution of intracellular organelles is a fundamental process in cells. Organelle motion is a complex phenomenon that depends on a large number of variables including the shape of the organelle, the type of motors with which the organelles are associated, and the mechanical properties of the cytoplasm. This paper presents a study that characterizes the diffusive motion of mitochondria in chondrocytes seeded in agarose constructs and what this implies about the mechanical properties of the cytoplasm. Method of approach: Images showing mitochondrial motion in individual cells at 30s intervals for 15min were captured with a confocal microscope. Digital image correlation was used to quantify the motion of the mitochondria, and the mean square displacement (MSD) was calculated. Statistical tools for testing whether the characteristic motion of mitochondria varied throughout the cell were developed. Calculations based on statistical mechanics were used to establish connections between the measured MSDs and the mechanical nature of the cytoplasm. Results: The average MSD of the mitochondria varied with time according to a power law with the power term greater than 1, indicating that mitochondrial motion can be viewed as a combination of diffusion and directional motion. Statistical analysis revealed that the motion of the mitochondria was not uniform throughout the cell, and that the diffusion coefficient may vary by over 50%, indicating intracellular heterogeneity. High correlations were found between movements of mitochondria when they were less than 2μm apart. The correlation is probably due to viscoelastic properties of the cytoplasm. Theoretical analysis based on statistical mechanics suggests that directed diffusion can only occur in a material that behaves like a fluid on large time scales. Conclusions: The study shows that mitochondria in different regions of the cell experience different characteristic motions. This suggests that the cytoplasm is a heterogeneous viscoelastic material. The study provides new insight into the motion of mitochondria in chondrocytes and its connection with the mechanical properties of the cytoplasm.

1.
Rojo
,
G.
,
Chamorro
,
M.
,
Salas
,
R. L.
,
Vinuela
,
E.
,
Cuezva
,
J. M.
, and
Salas
,
J.
, 1998, “
Migration of Mitochondria to Viral Assembly Sites in African Swine Fever Virus-Infected Cells
,”
J. Virol.
0022-538X,
72
(
9
), pp.
7583
7588
.
2.
Hallmann
,
A.
,
Milczarek
,
R.
,
Lipinski
,
M.
,
Kossowska
,
E.
,
Spodnik
,
J. H.
,
Wozniak
,
M.
,
Wakabayashi
,
T.
, and
Klimek
,
J.
, 2004, “
Fast Perinuclear Clustering of Mitochondria in Oxidatively Stressed Human Choriocarcinoma Cells
,”
Folia Morphol. (Warsaw)
0015-5659,
63
(
4
), pp.
407
412
.
3.
Saxton
,
M. J.
, and
Jacobson
,
K.
, 1997, “
Single Particle Tracking: Application to Membrane Dynamics
,”
Annu. Rev. Biophys. Biomol. Struct.
1056-8700,
26
, pp.
373
399
.
4.
Suh
,
J.
,
Dawson
,
M.
, and
Hanes
,
J.
, 2005, “
Real-Time Multiple-Particle Tracking: Applications to Drug and Gene Delivery
,”
Adv. Drug Delivery Rev.
0169-409X,
57
(
1
), pp.
63
78
.
5.
Ritchie
,
K.
,
Shan
,
X. Y.
,
Kondo
,
J.
,
Iwasawa
,
K.
,
Fujiwara
,
T.
, and
Kusumi
,
A.
, 2005, “
Detection of Non-Brownian Diffusion in The Cell Membrane in Single Molecule Tracking
,”
Biophys. J.
0006-3495,
88
(
3
), pp.
2266
2277
.
6.
Yamada
,
S.
,
Wirtz
,
D.
, and
Kuo
,
S. C.
, 2000, “
Mechanics of Living Cells Measured by Laser Tracking Microrheology
,”
Biophys. J.
0006-3495,
78
(
4
), pp.
1736
1747
.
7.
Tseng
,
Y.
,
Kole
,
T. P.
, and
Wirtz
,
D.
, 2002, “
Micromechanical Mapping of Live Cells by Multiple Particle Tracking Microrheology
,”
Biophys. J.
0006-3495,
83
(
6
), pp.
3162
3176
.
8.
Crocker
,
J. C.
,
Valentine
,
M. T.
,
Weeks
,
E. R.
,
Gisler
,
T.
,
Kaplan
,
P. D.
,
Yodh
,
A. G.
, and
Weitz
,
D. A.
, 2000, “
Two-Point Microrheology of Inhomogeneous Soft Materials
,”
Phys. Rev. Lett.
0031-9007,
85
(
4
), pp.
888
891
.
9.
Lau
,
A. W.
,
Hoffman
,
B. D.
,
Davies
,
A.
,
Crocker
,
J. C.
, and
Lubensky
,
T. C.
, 2003, “
Microrheology, Stress Fluctuations and Active Behavior of Living Cells
,”
Phys. Rev. Lett.
0031-9007,
91
(
19
), p.
198101
.
10.
Pereira
,
A. J.
,
Dalby
,
B.
,
Stewart
,
R. J.
,
Doxsey
,
S. J.
, and
Goldstein
,
L. S. B.
, 1997, “
Mitochondrial Association of a Plus End-Directed Microtubule Motor Expressed During Mitosis in Drosophila
,”
J. Cell Biol.
0021-9525,
136
(
5
), pp.
1081
1090
.
11.
Yaffe
,
M. P.
, 1999, “
The Machinery of Mitochondrial Inheritance and Behavior
,”
Science
0036-8075,
283
(
5407
), pp.
1493
1497
.
12.
Mullineaux
,
C. W.
, 2004, “
FRAP Analysis of Photosynthetic Membranes
,”
J. Exp. Bot.
0022-0957,
55
(
400
), pp.
1207
1211
.
13.
Kettling
,
U.
,
Koltermann
,
A.
,
Schwille
,
P.
, and
Eigen
,
M.
, 1998, “
Real-Time Enzyme Kinetics Monitored by Dual-Color Fluorescence Cross-Correlation Spectroscopy
,”
Proc. Natl. Acad. Sci. U.S.A.
0027-8424,
95
(
4
), pp.
1416
1420
.
14.
Knowles
,
M. K.
,
Guenza
,
M. G.
,
Capaldi
,
R. A.
, and
Marcus
,
A. H.
, 2002, “
Cytoskeletal-Assisted Dynamics of the Mitochondrial Reticulum in Living Cells
,”
Proc. Natl. Acad. Sci. U.S.A.
0027-8424,
99
(
23
), pp.
14772
14777
.
15.
Margineantu
,
D.
,
Capaldi
,
R. A.
, and
Marcus
,
A. H.
, 2000, “
Dynamics of the Mitochondrial Reticulum in Live Cells Using Fourier Image Correlation Spectroscopy and Digital Video Imaging
,”
Biophys. J.
0006-3495,
79
(
4
), pp.
1833
1849
.
16.
Lee
,
D. A.
, and
Bader
,
D. L.
, 1997, “
Compressive Strains at Physiological Frequencies Influence the Metabolism of Chondrocytes Seeded in Agarose
,”
J. Orthop. Res.
0736-0266,
15
(
2
), pp.
181
188
.
17.
Sawae
,
Y.
,
Shelton
,
J. C.
,
Bader
,
D. L.
, and
Knight
,
M. M.
, 2004, “
Confocal Analysis of Local and Cellular Strains in Chondrocyte-Agarose Constructs Subjected to Mechanical Shear
,”
Ann. Biomed. Eng.
0090-6964,
32
(
6
), pp.
860
870
.
18.
Wang
,
Y.
, and
Cuitino
,
A. M.
, 2002, “
Full-Field Measurements of Heterogeneous Deformation Patterns on Polymeric Foams Using Digital Image Correlation
,”
Int. J. Solids Struct.
0020-7683,
39
, pp.
3777
3796
.
19.
Chahine
,
N. O.
,
Wang
,
C. C.
,
Hung
,
C. T.
, and
Ateshian
,
G. A.
, 2004, “
Anisotropic Strain-Dependent Material Properties of Bovine Articular Cartilage in the Transitional Range From Tension to Compression
,”
J. Biomech.
0021-9290,
37
(
8
), pp.
1251
1261
.
20.
Wang
,
C. C.
,
Chahine
,
N. O.
,
Hung
,
C. T.
, and
Ateshian
,
G. A.
, 2003, “
Optical Determination of Anisotropic Material Properties of Bovine Articular Cartilage in Compression
,”
J. Biomech.
0021-9290,
36
(
3
), pp.
339
353
.
21.
McKinley
,
T. O.
, and
Bay
,
B. K.
, 2003, “
Trabecular Bone Strain Changes Associated with Subchondral Stiffening of the Proximal Tibia
,”
J. Biomech.
0021-9290,
36
(
2
), pp.
155
163
.
22.
Hu
,
S.
,
Chen
,
J.
,
Fabry
,
B.
,
Numaguchi
,
Y.
,
Gouldstone
,
A.
,
Ingber
,
D. E.
,
Fredberg
,
J. J.
,
Butler
,
J. P.
, and
Wang
,
N.
, 2003, “
Intracellular Stress Tomography Reveals Stress Focusing and Structural Anisotropy in Cytoskeleton of Living Cells
,”
Am. J. Physiol.: Cell Physiol.
0363-6143,
285
(
5
), pp.
C1082
-
C1090
.
23.
Knight
,
M. M.
,
Bomzon
,
Z.
,
Kimmel
,
E.
,
Sharma
,
A. M.
,
Lee
,
D. A.
, and
Bader
,
D. L.
, “
Chondrocyte Deformation Induces Mitochondrial Distortion and Heterogeneous Intracellular Strain Fields
,”
Biomech. Mod. Mech. Biol.
, in press.
24.
Valentine
,
M. T.
,
Kaplan
,
P. D.
,
Thota
,
D.
,
Crocker
,
J. C.
,
Gisler
,
T.
,
Prud’homme
,
R. K.
,
Beck
,
M.
, and
Weitz
,
D. A.
, 2001, “
Investigating the Microenvironment of Inhomogeneous Soft Materials with Multiple Particle Tracking
,”
Phys. Rev. E
1063-651X
64
(
6 Pt 1
), pp.
061506
061509
.
25.
Flugge
,
W.
, 1975,
Viscoelasticity
, 2nd rev ed.,
Springer
,
New York
.
26.
Mason
,
T. G.
,
Ganesan
,
K.
,
van Zanten
,
J. H.
,
Wirtz
,
D.
, and
Kuo
,
S. C.
, 1997, “
Particle Tracking Microrheology of Complex Fluids
,”
Phys. Rev. Lett.
0031-9007,
79
(
17
), pp.
3282
3285
.
27.
Apgar
,
J.
,
Tseng
,
Y.
,
Federov
,
E.
,
Herwig
,
M. B.
,
Almo
,
S. C.
, and
Wirtz
,
D.
, 2000, “
Multiple-Particle Tracking Measurements of heterogeneity of Actin Filaments and Actin Bundles
,”
Biophys. J.
0006-3495,
79
(
2
), pp.
1095
1106
.
28.
Tseng
,
Y.
, and
Wirtz
,
D.
, 2001, “
Mechanics and Multiple-Particle Tracking Microheterogeneiety of α-Actinin-Cross-Linked Actin Filament Networks
,”
Biophys. J.
0006-3495,
81
(
3
), pp.
1643
1658
.
29.
Kole
,
T. P.
,
Tseng
,
Y.
,
Jiang
,
I.
,
Katz
,
J. L.
, and
Wirtz
,
D.
, 2005, “
Intracellular Mechanics of Migrating Fibroblasts
,”
Mol. Biol. Cell
1059-1524,
16
, pp.
328
338
.
30.
Caspi
,
A.
,
Granek
,
R.
, and
Elabaum
,
M.
, 2000, “
Enhanced Diffusion in Active Cellular Transport
,”
Phys. Rev. Lett.
0031-9007,
85
(
26 pt. 1
), pp.
5655
5658
.
31.
Fabry
,
B.
,
Maksym
,
G. N.
,
Butler
,
J. P.
,
Glogauer
,
M.
,
Navajas
,
D.
, and
Fredberg
,
J. J.
, 2001, “
Scaling the Microrheology of Living Cells
,”
Phys. Rev. Lett.
0031-9007,
87
(
14
), p.
148102
.
32.
Bursac
,
P.
,
Lenormand
,
G.
,
Fabry
,
B.
,
Oliver
,
M.
,
Weitz
,
D. A.
,
Viasnoff
,
V.
,
Butler
,
J. P.
, and
Fredberg
,
J. J.
, 2005, “
Cytoskeletal Remodeling and Slow Dynamics in the Living Cell
,”
Nat. Mater.
1476-1122,
4
(
7
), pp.
557
561
.
33.
Trickey
,
W. R.
,
Vail
,
T. P.
, and
Guilak
,
F.
, 2004, “
The Role of The Cytoskeleton in the Viscoelastic Properties of Human Articular Chondrocytes
,”
J. Orthop. Res.
0736-0266,
22
(
1
), pp.
131
139
.
34.
Leipzig
,
N. D.
, and
Athanasiou
,
K. A.
, 2005, “
Unconfined Creep Compression of Chondrocytes
,”
J. Biomech.
0021-9290,
38
(
1
), pp.
77
85
.
35.
Knight
,
M. M.
,
van de Breevaart Bravenboer
,
J.
,
Lee
,
D. A.
,
van Osch
,
G. J.
,
Weinans
,
H.
, and
Bader
,
D. L.
, 2002, “
Cell and Nucleus Deformation in Compressed Chondrocyte-Alginate Constructs: Temporal Changes and Calculation of Cell Modulus
,”
Biochim. Biophys. Acta
0006-3002,
1570
(
1
), pp.
1
8
.
You do not currently have access to this content.