When Indiana visits Ohio State on Saturday, it’ll be a matchup of top-10 teams.

But it’ll also feature a heavy favorite vs. a heavy underdog. The Hoosiers are 20.5-point dogs going into Columbus, likely one of the biggest margins for two top-10 opponents in NCAA history.

Even though the No. 9 Hoosiers have earned the respect of many, they’re not yet expected to be able to keep up with national title contender Ohio State, a perennial power that is 3-0, ranked third and coming off a COVID-forced bye. IU, which beat Michigan State last Saturday to move to 4-0, is going to have to win some individual — or positional — battles to be able to pull off the upset and earn what would be its biggest victory in the last 50 years.

A look at 5 of IU’s must-win matchups:

1. Turnover margin

Finishing with a plus turnover margin is a goal of every team in every game, but it might be more acute Saturday because of the nature of the matchup. Indiana has thrived in turning the opposition’s miscues into points, to the tune of 57 points off  12 takeaways this season, including 17 points off 4 turnovers vs. the Spartans.

Indiana, which leads the Big Ten in interceptions (10) and sacks (12), is first in the Big Ten (tied for 3rd nationally) in takeaway margin (+8) and first in the league (20th nationally) in total takeaways (12). It’s picked up multiple interceptions in every game this season, including 2 vs. Pen State, 3 at Rutgers, 2 vs. Michigan and 3 against MSU. IU has at least one takeaway in 33 of its last 35 games.

Needless to say, it’s a big part of the Hoosiers’ formula for success, and a reason why their scoring (33.8 points per game, third in the Big Ten) is out-measuring their yardage (362.8, 10th); IU is taking advantage of the extra opportunities, many on short fields, to rack up points.

The problem Saturday — potentially — is that Ohio State isn’t generous with the football, having only 2 turnovers all season. Justin Fields has 11 touchdowns without a pick. The Buckeyes have put the ball on the turf 5 times, but lost only 2.

2. O-Line vs. Buckeyes D-line

The left side of the Hoosiers’ offensive line had a couple new faces against the Spartans, and it held up OK. Luke Haggard and Dylan Powell were in at left tackle and left guard, respectively, as Caleb Jones and Mike Katic were on the sidelines with injuries.

It wasn’t a perfect performance, as the Hoosiers struggled — again — to find a consistent running game and didn’t perform well in the red zone in the second half.

But Indiana has allowed only 2 sacks since giving up 3 to Penn State in the season-opener, although at least some of that is due to QB Michael Penix Jr.’s pocket awareness.

The Buckeyes have 9 sacks, third-most in the Big Ten, and the Hoosiers will be best served to keep an eye on veteran defensive tackle Tommy Togiai, who has a team-high 3.

3. DBs vs. OSU’s 2 standout receivers

Garrett Wilson and Chris Olave form one of the best receiving duos in the Big Ten, as they’ve combined for 42 receptions for 632 yards and 6 touchdowns. Olave averages 16 yards per reception and Wilson 14.3. It’s a deadly combination with Fields, who is hitting on a ridiculous 86.7 percent of his passes while averaging 12.6 per completion.

It’ll be the biggest challenge of the year for Indiana’s secondary, which has already proven to be one of the best in the Big Ten. Saturday will be nothing like the previous opponents, none of whom could even come close to the kind of offensive fireworks OSU is capable of.

Corner Tiawan Mullen, who has played at least at an All-Big Ten-level if not All-America, might need a gigantic game if the Hoosiers are to slow down the Ohio State passing attack.

4. Defense vs. Buckeyes’ runners

Ohio State has the Big Ten’s third-ranked rushing attack, so as if slowing down Fields and Co. wasn’t enough, IU’s defense has to try to stop the running game too.

Not easy.

OSU is averaging 208.7 yards per game.

But Indiana has been pleased with its defensive front of late, holding Michigan State to 60 yards rushing a week after limiting Michigan to 13.

If Indiana can make Ohio State one dimensional — and that’s a big ‘if’ — then perhaps it improves the Hoosiers’ chance to generate turnovers, extra possessions and a win.

5. Win the second quarter

As they say, something has to give in the second quarter.

Both teams have dominated the 15 minutes.

Indiana has shut out its opponents in the second quarters of all four of its games, winning 54-0. Ohio State has done nearly the same, outscoring its three opponents 45-10 while outgaining them by more than a 4-to-1 margin.

In Ohio State’s last outing two weeks ago — Maryland canceled last Saturday due to a COVID outbreak — the Buckeyes outgained Rutgers 194-11 in the second quarter.

If Indiana can win the quarter and take momentum into halftime, it would go a long way toward the upset.